Trial Outcomes & Findings for Study to Assess Safety & Efficacy of Sitagliptin as Initial Oral Therapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants. (MK-0431-083) (NCT NCT01485614)

NCT ID: NCT01485614

Last Updated: 2022-09-23

Results Overview

Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 200 participants
• Primary outcome timeframe: Baseline and Week 20
• Results posted on: 2022-09-23

Participant Flow

The study recruited participants in clinics/clinical offices in 42 countries.

Participants in a one-week, run-in received sitagliptin placebo prior to morning meals and metformin placebo prior to morning and evening meals. Participants enrolled in the metformin and placebo/sitagliptin arms prior to implementation of Protocol Amendment 05 completed the study on their original treatment assignments.

Participant milestones

Measure	Sitagliptin Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.
Randomization STARTED	96	90	9	5
Randomization COMPLETED	95	90	9	5
Randomization NOT COMPLETED	1	0	0	0
Weeks 0-20 STARTED	95	90	9	5
Weeks 0-20 Treated	95	90	9	5
Weeks 0-20 COMPLETED	85	86	8	5
Weeks 0-20 NOT COMPLETED	10	4	1	0
Weeks 20-54 STARTED	85	86	8	5
Weeks 20-54 COMPLETED	74	78	6	5
Weeks 20-54 NOT COMPLETED	11	8	2	0

Reasons for withdrawal

Measure	Sitagliptin Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.
Randomization Not Treated	1	0	0	0
Weeks 0-20 Lost to Follow-up	2	0	0	0
Weeks 0-20 Withdrawal by Parent/Guardian	5	2	0	0
Weeks 0-20 Withdrawal by Subject	3	2	1	0
Weeks 20-54 Lost to Follow-up	4	3	1	0
Weeks 20-54 Withdrawal by Parent/Guardian	2	2	1	0
Weeks 20-54 Withdrawal by Subject	5	3	0	0

Baseline Characteristics

Study to Assess Safety & Efficacy of Sitagliptin as Initial Oral Therapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants. (MK-0431-083)

Baseline characteristics by cohort

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Total n=199 Participants Total of all reporting groups
Age, Continuous	14.3 years STANDARD_DEVIATION 2.0 • n=93 Participants	13.7 years STANDARD_DEVIATION 1.9 • n=4 Participants	13.3 years STANDARD_DEVIATION 3.0 • n=27 Participants	15.0 years STANDARD_DEVIATION 1.6 • n=483 Participants	14.0 years STANDARD_DEVIATION 2.0 • n=36 Participants
Age, Customized In utero	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Customized Preterm newborn infants (gestational age < 37 wks)	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Customized Newborns (0-27 days)	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Customized Infants and toddlers (28 days-23 months)	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Customized Children (2-11 years)	11 Participants n=93 Participants	11 Participants n=4 Participants	3 Participants n=27 Participants	0 Participants n=483 Participants	25 Participants n=36 Participants
Age, Customized Adolescents (12-17 years)	84 Participants n=93 Participants	79 Participants n=4 Participants	6 Participants n=27 Participants	5 Participants n=483 Participants	174 Participants n=36 Participants
Age, Customized Adults (18-64 years)	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Customized From 65-84 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Customized 85 years and over	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Customized Unknown	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Sex: Female, Male Female	54 Participants n=93 Participants	58 Participants n=4 Participants	6 Participants n=27 Participants	3 Participants n=483 Participants	121 Participants n=36 Participants
Sex: Female, Male Male	41 Participants n=93 Participants	32 Participants n=4 Participants	3 Participants n=27 Participants	2 Participants n=483 Participants	78 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=93 Participants	33 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants	73 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants n=93 Participants	54 Participants n=4 Participants	5 Participants n=27 Participants	3 Participants n=483 Participants	115 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	0 Participants n=483 Participants	11 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=93 Participants	9 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	15 Participants n=36 Participants
Race (NIH/OMB) Asian	13 Participants n=93 Participants	14 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	30 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	8 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	11 Participants n=36 Participants
Race (NIH/OMB) White	48 Participants n=93 Participants	47 Participants n=4 Participants	6 Participants n=27 Participants	3 Participants n=483 Participants	104 Participants n=36 Participants
Race (NIH/OMB) More than one race	20 Participants n=93 Participants	18 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	39 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Glycated Hemoglobin (A1C)	7.43 Percentage STANDARD_DEVIATION 1.02 • n=93 Participants	7.56 Percentage STANDARD_DEVIATION 1.08 • n=4 Participants	7.43 Percentage STANDARD_DEVIATION 1.07 • n=27 Participants	8.02 Percentage STANDARD_DEVIATION 0.75 • n=483 Participants	7.50 Percentage STANDARD_DEVIATION 1.04 • n=36 Participants
Fasting Plasma Glucose	138.4 mg/dL STANDARD_DEVIATION 47.2 • n=93 Participants	138.6 mg/dL STANDARD_DEVIATION 42.8 • n=4 Participants	134.6 mg/dL STANDARD_DEVIATION 59.1 • n=27 Participants	142.2 mg/dL STANDARD_DEVIATION 38.7 • n=483 Participants	138.6 mg/dL STANDARD_DEVIATION 44.7 • n=36 Participants

PRIMARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C.

Outcome measures

Measure	Sitagliptin n=78 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=70 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Hemoglobin A1C (A1C) at Week 20	-0.13 Percentage Standard Deviation 1.58 • Interval 1.58 to	-0.02 Percentage Standard Deviation 1.45 • Interval 1.45 to	-1.03 Percentage Standard Deviation 0.72 • Interval 0.72 to	0.57 Percentage Standard Deviation 1.62 • Interval 1.62 to

PRIMARY outcome

Timeframe: Baseline

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Baseline Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm	7.58 Percentage Standard Deviation 1.06	—	—	—

PRIMARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C from a longitudinal data analysis (LDA) model. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The Statistical Analysis Plan (SAP) did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=95 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))	-0.01 Percentage Interval -0.35 to 0.34	0.18 Percentage Interval -0.17 to 0.53	—	—

PRIMARY outcome

Timeframe: Up to Week 56

Population: The analysis population includes all randomized participants who received ≥1 dose of study medication.

The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56	73 Participants	67 Participants	7 Participants	4 Participants

PRIMARY outcome

Timeframe: Up to Week 56

Population: The analysis population includes all randomized participants who received ≥1 dose of study medication. Participants (n=5) from the Placebo/Sitagliptin arm were excluded because sitagliptin received during Week 0-54 was an inappropriate control for the Sitagliptin arm which received sitagliptin during both study treatment phases.

The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)	76.8 Percentage of participants	74.4 Percentage of participants	—	—

PRIMARY outcome

Timeframe: Up to Week 54

Population: The analysis population includes all randomized participants who received ≥1 dose of study medication.

The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54	5 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Week 54

Population: The analysis population includes all randomized participants who received ≥1 dose of study medication. Participants (n=5) from the Placebo/Sitagliptin arm were excluded because sitagliptin received during Week 0-54 was an inappropriate control for the Sitagliptin arm which received sitagliptin during both study treatment phases.

The percentage of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)	5.3 Percentage of participants	1.1 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants who took at least one dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. This change from baseline reflects the Week 54 A1C minus the Week 0 A1C.

Outcome measures

Measure	Sitagliptin n=41 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=48 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in A1C at Week 54	-0.19 Percentage Standard Deviation 1.37	-0.90 Percentage Standard Deviation 1.41	-0.70 Percentage Standard Deviation 0.94	-0.50 Percentage Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants With A1C at Goal (<7.0%) at Week 20	49.5 Percentage of Participants	37.8 Percentage of Participants	77.8 Percentage of Participants	20.0 Percentage of Participants

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=95 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))	49.5 Percentage of participants	36.8 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants With A1C at Goal (<6.5%) at Week 20	30.5 Percentage of participants	23.3 Percentage of participants	66.7 Percentage of participants	20.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=95 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))	30.5 Percentage of Participants	23.2 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants with A1C at goal (<7.0%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants With A1C at Goal (<7.0%) at Week 54	28.4 Percentage of participants	40.0 Percentage of participants	33.3 Percentage of participants	20.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants with A1C at goal (<6.5%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants With A1C at Goal (<6.5%) at Week 54	20.0 Percentage of participants	35.6 Percentage of participants	22.2 Percentage of participants	20.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.

Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline.

Outcome measures

Measure	Sitagliptin n=81 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=74 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20	9.98 mg/dL Standard Deviation 61.86 • Interval 61.86 to	7.59 mg/dL Standard Deviation 41.11 • Interval 41.11 to	-19.88 mg/dL Standard Deviation 49.78 • Interval 49.78 to	57.67 mg/dL Standard Deviation 51.05 • Interval 51.05 to

SECONDARY outcome

Timeframe: Baseline

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at baseline.

Blood glucose was measured on a fasting basis. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Baseline Fasting Plasma Glucose (FPG) for the Placebo (Pooled) Arm	138.8 mg/dL Standard Deviation 42.4	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline and was estimated from a longitudinal data analysis model. The current outcome measure focused on results from participants randomized to sitagliptin or placebo. The Week 20 treatment comparison of Sitagliptin vs Placebo included all participants treated with Sitagliptin or Placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=95 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))	7.2 mg/dL Interval -4.2 to 18.7	5.7 mg/dL Interval -6.0 to 17.4	—	—

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.

Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 54 minus FPG at baseline.

Outcome measures

Measure	Sitagliptin n=44 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=51 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=6 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in FPG at Week 54	-3.03 mg/dL Standard Deviation 48.55	-4.52 mg/dL Standard Deviation 50.68	-29.92 mg/dL Standard Deviation 53.19	3.00 mg/dL Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 20.

PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour PMG minus the Week 0 2-hour PMG.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20	-2.9 mg/dL Standard Deviation 42.6 • Interval 42.6 to	2.1 mg/dL Standard Deviation 72.1 • Interval 72.1 to	-6.8 mg/dL Standard Deviation 21.1 • Interval 21.1 to	63.5 mg/dL Standard Deviation 171.8 • Interval 171.8 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 54.

PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour PMG minus the Week 0 2-hour PMG.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in 2-hour PMG at Week 54	-1.7 mg/dL Standard Deviation 21.3	-16.8 mg/dL Standard Deviation 48.9	-39.7 mg/dL Standard Deviation 32.3	-28.0 mg/dL Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 20.

2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour incremental PMG minus the Week 0 2-hour incremental PMG.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in 2-hour Incremental PMG at Week 20	1.5 mg/dL Standard Deviation 55.3 • Interval 55.3 to	0.7 mg/dL Standard Deviation 35.9 • Interval 35.9 to	0.8 mg/dL Standard Deviation 15.6 • Interval 15.6 to	12.5 mg/dL Standard Deviation 98.3 • Interval 98.3 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 54.

2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour incremental PMG minus the Week 0 2-hour incremental PMG.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in 2-Hour Incremental PMG at Week 54	-0.6 mg/dL Standard Deviation 64.6	-26.6 mg/dL Standard Deviation 39.0	-31.3 mg/dL Standard Deviation 34.8	-32.0 mg/dL Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

This change from baseline reflects the Week 20 insulin minus the Week 0 insulin.

Outcome measures

Measure	Sitagliptin n=67 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=58 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=7 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin	1.59 mIU/L Standard Deviation 47.24 • Interval 47.24 to	-3.91 mIU/L Standard Deviation 22.31 • Interval 22.31 to	-7.25 mIU/L Standard Deviation 60.58 • Interval 60.58 to	-1.23 mIU/L Standard Deviation 20.55 • Interval 20.55 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.

This change from baseline reflects the Week 54 insulin minus the Week 0 insulin.

Outcome measures

Measure	Sitagliptin n=37 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=45 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin	-9.65 mIU/L Standard Deviation 40.82	-6.64 mIU/L Standard Deviation 32.01	-20.50 mIU/L Standard Deviation 65.08	-9.95 mIU/L Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.

This change from baseline reflects the Week 20 proinsulin minus the Week 0 proinsulin.

Outcome measures

Measure	Sitagliptin n=68 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=57 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=7 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin	0.91 pmol/L Standard Deviation 81.88 • Interval 81.88 to	-10.88 pmol/L Standard Deviation 55.12 • Interval 55.12 to	12.57 pmol/L Standard Deviation 36.98 • Interval 36.98 to	-1.33 pmol/L Standard Deviation 9.07 • Interval 9.07 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.

This change from baseline reflects the Week 54 proinsulin minus the Week 0 proinsulin.

Outcome measures

Measure	Sitagliptin n=38 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=42 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin	-10.62 pmol/L Standard Deviation 67.54	-16.13 pmol/L Standard Deviation 81.52	-23.30 pmol/L Standard Deviation 42.36	-0.50 pmol/L Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.

Change from baseline was the Week 20 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.

Outcome measures

Measure	Sitagliptin n=65 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=55 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=6 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin	0.02 Ratio Standard Deviation 0.22 • Interval 0.22 to	0.02 Ratio Standard Deviation 0.16 • Interval 0.16 to	-0.03 Ratio Standard Deviation 0.10 • Interval 0.1 to	-0.19 Ratio Standard Deviation 0.45 • Interval 0.45 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.

The change from baseline was Week 54 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.

Outcome measures

Measure	Sitagliptin n=36 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=41 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin	0.02 Ratio Standard Deviation 0.23	-0.03 Ratio Standard Deviation 0.19	-0.01 Ratio Standard Deviation 0.06	0.02 Ratio Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.

HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. The change from baseline was Week 20 HOMA-β minus the Week 0 HOMA-β.

Outcome measures

Measure	Sitagliptin n=67 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=58 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=7 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin	15.72 Percentage of Beta Cell Function Standard Deviation 162.47 • Interval 162.47 to	-53.23 Percentage of Beta Cell Function Standard Deviation 296.23 • Interval 296.23 to	-1757.50 Percentage of Beta Cell Function Standard Deviation 4765.46 • Interval 4765.46 to	-64.78 Percentage of Beta Cell Function Standard Deviation 126.65 • Interval 126.65 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.

HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. This change from baseline was Week 54 HOMA-β minus the Week 0 HOMA-β.

Outcome measures

Measure	Sitagliptin n=36 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=45 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin	-41.15 Percentage of Beta Cell Function Standard Deviation 183.17	-63.88 Percentage of Beta Cell Function Standard Deviation 339.74	-1860.69 Percentage of Beta Cell Function Standard Deviation 4099.22	-121.48 Percentage of Beta Cell Function Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.

HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 20 HOMA-IR minus the Week 0 HOMA-IR.

Outcome measures

Measure	Sitagliptin n=67 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=58 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=7 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin	-0.50 Index of insulin resistance Standard Deviation 31.62 • Interval 31.62 to	-0.86 Index of insulin resistance Standard Deviation 9.02 • Interval 9.02 to	-4.46 Index of insulin resistance Standard Deviation 34.65 • Interval 34.65 to	2.58 Index of insulin resistance Standard Deviation 9.30 • Interval 9.3 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.

HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 54 HOMA-IR minus the Week 0 HOMA-IR.

Outcome measures

Measure	Sitagliptin n=36 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=45 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin	-6.13 Index of insulin resistance Standard Deviation 34.86	-1.30 Index of insulin resistance Standard Deviation 15.31	-15.18 Index of insulin resistance Standard Deviation 36.41	-2.21 Index of insulin resistance Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20	-49.3 mg*hr/dL Standard Deviation 103.6 • Interval 103.6 to	2.0 mg*hr/dL Standard Deviation 190.0 • Interval 190.0 to	18.6 mg*hr/dL Standard Deviation 50.9 • Interval 50.9 to	191.0 mg*hr/dL Standard Deviation 434.2 • Interval 434.2 to

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin 3-hour AUC at Week 20	-14.5 µIU*hr/mL Standard Deviation 128.0 • Interval 128.0 to	-32.8 µIU*hr/mL Standard Deviation 99.9 • Interval 99.9 to	141.7 µIU*hr/mL Standard Deviation 206.1 • Interval 206.1 to	-145.6 µIU*hr/mL Standard Deviation 180.6 • Interval 180.6 to

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in C-peptide 3-Hour AUC at Week 20	-1.8 ng*hr/mL Standard Deviation 4.9 • Interval 4.9 to	-0.1 ng*hr/mL Standard Deviation 3.3 • Interval 3.3 to	5.9 ng*hr/mL Standard Deviation 7.6 • Interval 7.6 to	-6.4 ng*hr/mL Standard Deviation 7.1 • Interval 7.1 to

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin total AUC/glucose total AUC ratio minus the Week 0 insulin total AUC/glucose total AUC ratio.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20	0.0 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation 0.3 • Interval 0.3 to	-0.1 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation 0.3 • Interval 0.3 to	0.2 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation 0.4 • Interval 0.4 to	-0.2 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation 0.3 • Interval 0.3 to

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20	-43.5 mg*hr/dL Standard Deviation 97.4 • Interval 97.4 to	10.8 mg*hr/dL Standard Deviation 58.6 • Interval 58.6 to	39.8 mg*hr/dL Standard Deviation 50.1 • Interval 50.1 to	46.2 mg*hr/dL Standard Deviation 201.9 • Interval 201.9 to

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20	-12.4 µIU*hr/mL Standard Deviation 89.4 • Interval 89.4 to	-19.4 µIU*hr/mL Standard Deviation 93.6 • Interval 93.6 to	87.5 µIU*hr/mL Standard Deviation 124.5 • Interval 124.5 to	-82.8 µIU*hr/mL Standard Deviation 93.4 • Interval 93.4 to

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=12 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=12 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20	-1.1 ng*hr/ml Standard Deviation 3.1 • Interval 3.1 to	-0.4 ng*hr/ml Standard Deviation 4.4 • Interval 4.4 to	4.1 ng*hr/ml Standard Deviation 5.6 • Interval 5.6 to	-4.8 ng*hr/ml Standard Deviation 5.2 • Interval 5.2 to

SECONDARY outcome

Timeframe: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio.

Outcome measures

Measure	Sitagliptin n=11 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=10 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20	2.2 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation 9.6 • Interval 9.6 to	7.2 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation 17.5 • Interval 17.5 to	-2.5 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation 3.2 • Interval 3.2 to	1.4 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation 2.2 • Interval 2.2 to

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Glucose 3-Hour AUC at Week 54	-21.1 mg*hr/dL Standard Deviation 47.7	-36.0 mg*hr/dL Standard Deviation 136.1	-73.1 mg*hr/dL Standard Deviation 95.8	-63.3 mg*hr/dL Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin 3-Hour AUC at Week 54	-43.2 µIU*hr/mL Standard Deviation 259.8	-253.9 µIU*hr/mL Standard Deviation 282.7	-37.8 µIU*hr/mL Standard Deviation 9.4	-184.4 µIU*hr/mL Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in C-peptide 3-Hour AUC at Week 54	-0.1 ng*hr/ml Standard Deviation 5.7	-6.1 ng*hr/ml Standard Deviation 8.2	1.7 ng*hr/ml Standard Deviation 1.0	-8.9 ng*hr/ml Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC/glucose 3-hour AUC ratio minus the Week 0 insulin 3-hour AUC/glucose 3-hour AUC ratio.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54	-0.1 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation 0.5	-0.6 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation 0.8	-0.0 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation 0.2	-0.3 [μIU*hr/mL]/[mg*hr/dL] Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54	-30.7 mg*hr/dL Standard Deviation 100.7	-50.1 mg*hr/dL Standard Deviation 79.5	-49.0 mg*hr/dL Standard Deviation 87.5	-74.0 mg*hr/dL Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54	-103.8 µIU*hr/mL Standard Deviation 151.0	-198.5 µIU*hr/mL Standard Deviation 263.0	-40.2 µIU*hr/mL Standard Deviation 11.5	-116.6 µIU*hr/mL Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54	-1.8 ng*hr/ml Standard Deviation 3.0	-5.2 ng*hr/ml Standard Deviation 8.8	0.9 ng*hr/ml Standard Deviation 0.5	-5.9 ng*hr/ml Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Population: The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.

AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio.

Outcome measures

Measure	Sitagliptin n=7 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=6 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54	4.1 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation 13.1	3.7 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation 5.6	-2.7 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation 4.3	1.4 [µIU*hr/mL]/[mg*hr/dL] Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Up to Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20	5.3 Percentage of participants	11.1 Percentage of participants	0.0 Percentage of participants	40.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication.

The percentage of participants who initiated glycemic rescue therapy prior to Week 54 was reported.

Outcome measures

Measure	Sitagliptin n=95 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=90 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=9 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54	35.8 Percentage of participants	28.9 Percentage of participants	11.1 Percentage of participants	80.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

This change from baseline was Week 20 BMI minus the Week 0 BMI.

Outcome measures

Measure	Sitagliptin n=84 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=82 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Body Mass Index (BMI) at Week 20	0.0 kg/m^2 Standard Deviation 2.2 • Interval 2.2 to	-0.7 kg/m^2 Standard Deviation 1.9 • Interval 1.9 to	-0.8 kg/m^2 Standard Deviation 1.4 • Interval 1.4 to	-1.7 kg/m^2 Standard Deviation 2.8 • Interval 2.8 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

This change from baseline was Week 54 BMI minus the Week 0 BMI.

Outcome measures

Measure	Sitagliptin n=72 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=73 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=6 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in BMI at Week 54	-0.4 kg/m^2 Standard Deviation 2.9	-1.0 kg/m^2 Standard Deviation 2.9	-0.6 kg/m^2 Standard Deviation 1.3	-0.3 kg/m^2 Standard Deviation 1.6

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

The percent change from baseline in CD26 = ([CD26 value at Week 20] - [baseline CD26 value]) ÷ baseline CD26 value × 100.

Outcome measures

Measure	Sitagliptin n=68 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=57 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20	4.06 Percent Change Standard Deviation 19.25 • Interval 19.25 to	-1.78 Percent Change Standard Deviation 17.18 • Interval 17.18 to	4.89 Percent Change Standard Deviation 1.90 • Interval 1.9 to	14.57 Percent Change Standard Deviation 15.46 • Interval 15.46 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

The percent change from baseline in CD26 = ([CD26 value at Week 54] - [baseline CD26 value]) ÷ baseline CD26 value × 100.

Outcome measures

Measure	Sitagliptin n=56 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=55 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54	4.74 Percent Change Standard Deviation 17.18	4.27 Percent Change Standard Deviation 18.24	12.63 Percent Change Standard Deviation 13.02	-5.30 Percent Change Standard Deviation 4.19

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin.

Outcome measures

Measure	Sitagliptin n=43 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=46 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Calcitonin at Week 20 - Females	-0.1 ng/L Standard Deviation 0.5 • Interval 0.5 to	-2.0 ng/L Standard Deviation 11.7 • Interval 11.7 to	0.0 ng/L Standard Deviation 0.0 • Interval 0.0 to	0.0 ng/L Standard Deviation 0.0 • Interval 0.0 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin.

Outcome measures

Measure	Sitagliptin n=30 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=43 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Calcitonin at Week 54 - Females	-1.0 ng/L Standard Deviation 0.6	-1.9 ng/L Standard Deviation 12.1	0.0 ng/L Standard Deviation 0.0	0.3 ng/L Standard Deviation 0.4

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin.

Outcome measures

Measure	Sitagliptin n=35 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=25 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Calcitonin at Week 20 - Males	0.2 ng/L Standard Deviation 1.4 • Interval 1.4 to	-0.2 ng/L Standard Deviation 0.6 • Interval 0.6 to	-1.6 ng/L Standard Deviation 2.2 • Interval 2.2 to	0.5 ng/L Standard Deviation 0.6 • Interval 0.6 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin.

Outcome measures

Measure	Sitagliptin n=33 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=21 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Calcitonin at Week 54 - Males	0.1 ng/L Standard Deviation 1.1	-0.3 ng/L Standard Deviation 0.9	0.0 ng/L Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	1.4 ng/L Standard Deviation 0.3

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents

Outcome measures

Measure	Sitagliptin n=33 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=31 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females	-28.7 nmol(BCE)/mmol(creatinine) Standard Deviation 120.9 • Interval 120.9 to	-41.2 nmol(BCE)/mmol(creatinine) Standard Deviation 148.9 • Interval 148.9 to	-98.0 nmol(BCE)/mmol(creatinine) Standard Deviation 153.0 • Interval 153.0 to	12.7 nmol(BCE)/mmol(creatinine) Standard Deviation 29.2 • Interval 29.2 to

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents

Outcome measures

Measure	Sitagliptin n=31 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=21 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males	-30.9 nmol(BCE)/mmol(creatinine) Standard Deviation 167.2	-69.8 nmol(BCE)/mmol(creatinine) Standard Deviation 162.1	62.0 nmol(BCE)/mmol(creatinine) Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	-29.0 nmol(BCE)/mmol(creatinine) Standard Deviation 32.5

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. Bone Collagen Equivalents

Outcome measures

Measure	Sitagliptin n=28 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=30 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females	-88.4 nmol(BCE)/mmol(creatinine) Standard Deviation 102.6	-61.2 nmol(BCE)/mmol(creatinine) Standard Deviation 137.6	-80.3 nmol(BCE)/mmol(creatinine) Standard Deviation 208.5	-17.0 nmol(BCE)/mmol(creatinine) Standard Deviation 13.5

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. All participants in the Metformin arm were missing baseline or Week 54 measurements. BCE = Bone Collagen Equivalents

Outcome measures

Measure	Sitagliptin n=30 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=16 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males	-78.2 nmol(BCE)/mmol(creatinine) Standard Deviation 166.9	-102.4 nmol(BCE)/mmol(creatinine) Standard Deviation 267.7	—	-30.0 nmol(BCE)/mmol(creatinine) Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.

Outcome measures

Measure	Sitagliptin n=43 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=52 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females	-6.0 μg/L Standard Deviation 13.7 • Interval 13.7 to	-4.2 μg/L Standard Deviation 9.9 • Interval 9.9 to	-9.7 μg/L Standard Deviation 7.7 • Interval 7.7 to	10.7 μg/L Standard Deviation 9.7 • Interval 9.7 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.

Outcome measures

Measure	Sitagliptin n=30 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=43 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females	-20.0 μg/L Standard Deviation 28.4	-13.5 μg/L Standard Deviation 18.1	-14.9 μg/L Standard Deviation 10.3	-6.9 μg/L Standard Deviation 9.2

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.

Outcome measures

Measure	Sitagliptin n=36 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=25 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males	-2.2 μg/L Standard Deviation 21.6 • Interval 21.6 to	0.1 μg/L Standard Deviation 19.9 • Interval 19.9 to	-7.1 μg/L Standard Deviation 0.2 • Interval 0.2 to	4.7 μg/L Standard Deviation 8.2 • Interval 8.2 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.

Outcome measures

Measure	Sitagliptin n=33 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=20 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males	-16.2 μg/L Standard Deviation 28.0	-15.0 μg/L Standard Deviation 27.0	-1.3 μg/L Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	-15.3 μg/L Standard Deviation 12.4

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.

Outcome measures

Measure	Sitagliptin n=38 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=49 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females	0.5 Percent Change Standard Deviation 21.9 • Interval 21.9 to	11.0 Percent Change Standard Deviation 34.0 • Interval 34.0 to	-3.2 Percent Change Standard Deviation 14.9 • Interval 14.9 to	41.4 Percent Change Standard Deviation 31.2 • Interval 31.2 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.

Outcome measures

Measure	Sitagliptin n=30 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=42 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in IGF-1 at Week 54 - Females	-1.5 Percent Change Standard Deviation 34.4	7.2 Percent Change Standard Deviation 57.6	-11.9 Percent Change Standard Deviation 13.4	-13.5 Percent Change Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.

Outcome measures

Measure	Sitagliptin n=36 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=20 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in IGF-1 at Week 20 - Males	-2.7 Percent Change Standard Deviation 22.1 • Interval 22.1 to	9.3 Percent Change Standard Deviation 29.6 • Interval 29.6 to	7.6 Percent Change Standard Deviation 17.4 • Interval 17.4 to	5.3 Percent Change Standard Deviation 16.2 • Interval 16.2 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.

Outcome measures

Measure	Sitagliptin n=32 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=18 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in IGF-1 at Week 54 - Males	-4.9 Percent Change Standard Deviation 33.5	29.6 Percent Change Standard Deviation 99.8	18.8 Percent Change Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	-6.8 Percent Change Standard Deviation 22.1

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.

Outcome measures

Measure	Sitagliptin n=41 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=50 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=6 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females	3.5 Percent Change Standard Deviation 18.2 • Interval 18.2 to	3.8 Percent Change Standard Deviation 13.8 • Interval 13.8 to	8.4 Percent Change Standard Deviation 12.9 • Interval 12.9 to	-0.7 Percent Change Standard Deviation 24.1 • Interval 24.1 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.

Outcome measures

Measure	Sitagliptin n=31 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=45 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in IGF-BP3 at Week 54 - Females	2.0 Percent Change Standard Deviation 16.7	4.5 Percent Change Standard Deviation 17.0	11.4 Percent Change Standard Deviation 17.4	-13.4 Percent Change Standard Deviation 9.9

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.

Outcome measures

Measure	Sitagliptin n=36 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=24 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in IGF-BP3 at Week 20 - Males	5.6 Percent Change Standard Deviation 13.3 • Interval 13.3 to	10.2 Percent Change Standard Deviation 18.6 • Interval 18.6 to	3.3 Percent Change Standard Deviation 0.5 • Interval 0.5 to	14.2 Percent Change Standard Deviation 50.6 • Interval 50.6 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.

Outcome measures

Measure	Sitagliptin n=32 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=21 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Percent Change From Baseline in IGF-BP3 at Week 54 - Males	5.4 Percent Change Standard Deviation 18.4	18.2 Percent Change Standard Deviation 43.1	-2.9 Percent Change Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	22.5 Percent Change Standard Deviation 8.3

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 20.

Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).

Outcome measures

Measure	Sitagliptin n=46 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=53 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=6 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Growth Velocity at Week 20 - Females	3.2 cm/year Standard Deviation 8.2 • Interval 8.2 to	1.9 cm/year Standard Deviation 2.7 • Interval 2.7 to	5.0 cm/year Standard Deviation 6.8 • Interval 6.8 to	0.6 cm/year Standard Deviation 1.6 • Interval 1.6 to

SECONDARY outcome

Timeframe: Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 54.

Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).

Outcome measures

Measure	Sitagliptin n=37 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=48 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Growth Velocity at Week 54 - Females	2.1 cm/year Standard Deviation 3.7	1.2 cm/year Standard Deviation 1.8	2.4 cm/year Standard Deviation 2.9	0.7 cm/year Standard Deviation 1.0

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 20.

Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).

Outcome measures

Measure	Sitagliptin n=38 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=29 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Growth Velocity at Week 20 - Males	2.6 cm/year Standard Deviation 2.7 • Interval 2.7 to	3.6 cm/year Standard Deviation 3.2 • Interval 3.2 to	-1.0 cm/year Standard Deviation 1.3 • Interval 1.3 to	1.7 cm/year Standard Deviation 2.4 • Interval 2.4 to

SECONDARY outcome

Timeframe: Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 54.

Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).

Outcome measures

Measure	Sitagliptin n=35 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=25 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Growth Velocity at Week 54 - Males	2.5 cm/year Standard Deviation 2.5	2.8 cm/year Standard Deviation 2.1	1.7 cm/year Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	2.8 cm/year Standard Deviation 4.0

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 20.

Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from an X-ray of left hand and wrist.

Outcome measures

Measure	Sitagliptin n=17 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=18 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Skeletal Maturation at Week 20 - Females	0.6 Ratio Standard Deviation 1.9 • Interval 1.9 to	0.4 Ratio Standard Deviation 1.8 • Interval 1.8 to	1.7 Ratio Standard Deviation 2.3 • Interval 2.3 to	-0.8 Ratio Standard Deviation 5.5 • Interval 5.5 to

SECONDARY outcome

Timeframe: Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 54.

Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Placebo/Sitagliptin arm were missing baseline or Week 54 measurements.

Outcome measures

Measure	Sitagliptin n=8 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=14 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Skeletal Maturation at Week 54 - Females	1.3 Ratio Standard Deviation 1.1	1.0 Ratio Standard Deviation 0.6	1.3 Ratio Standard Deviation 2.2	—

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 20.

Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist.

Outcome measures

Measure	Sitagliptin n=13 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=17 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Skeletal Maturation at Week 20 - Males	1.6 Ratio Standard Deviation 1.7	1.2 Ratio Standard Deviation 1.1	0.4 Ratio Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	2.4 Ratio Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.

SECONDARY outcome

Timeframe: Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 54.

Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Metformin and Placebo/Sitagliptin arms were missing baseline or Week 54 measurements.

Outcome measures

Measure	Sitagliptin n=11 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=10 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Skeletal Maturation at Week 54 - Males	1.3 Ratio Standard Deviation 0.9	1.3 Ratio Standard Deviation 0.6	—	—

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 20 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia.

Outcome measures

Measure	Sitagliptin n=31 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=29 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males	0.3 Score on a scale Standard Deviation 0.5	0.2 Score on a scale Standard Deviation 0.4	0.0 Score on a scale Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	0.5 Score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 54 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. All participants in the Metformin arm were missing baseline or Week 54 measurements.

Outcome measures

Measure	Sitagliptin n=26 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=23 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males	0.5 Score on a scale Standard Deviation 0.6	0.6 Score on a scale Standard Deviation 0.7	—	0.6 Score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 20 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts.

Outcome measures

Measure	Sitagliptin n=38 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=44 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Staging for Breasts at Week 20 - Females	0.2 Score on a Scale Standard Deviation 0.6 • Interval 0.6 to	0.1 Score on a Scale Standard Deviation 0.3 • Interval 0.3 to	0.2 Score on a Scale Standard Deviation 0.4 • Interval 0.4 to	0.3 Score on a Scale Standard Deviation 0.6 • Interval 0.6 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 54 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts.

Outcome measures

Measure	Sitagliptin n=28 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=36 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Staging for Breasts at Week 54 - Females	0.5 Score on a Scale Standard Deviation 0.7	0.4 Score on a Scale Standard Deviation 0.6	0.5 Score on a Scale Standard Deviation 1.0	0.7 Score on a Scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.

Outcome measures

Measure	Sitagliptin n=38 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=43 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females	0.1 Score on a scale Standard Deviation 0.4 • Interval 0.4 to	0.1 Score on a scale Standard Deviation 0.3 • Interval 0.3 to	0.2 Score on a scale Standard Deviation 0.4 • Interval 0.4 to	0.0 Score on a scale Standard Deviation 0.0 • Interval 0.0 to

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.

Outcome measures

Measure	Sitagliptin n=28 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=35 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=4 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=3 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females	0.5 Score on a scale Standard Deviation 0.6	0.3 Score on a scale Standard Deviation 0.5	0.8 Score on a scale Standard Deviation 1.5	0.3 Score on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.

Outcome measures

Measure	Sitagliptin n=32 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=29 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=1 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males	0.3 Score on a scale Standard Deviation 0.5	0.2 Score on a scale Standard Deviation 0.4	0.0 Score on a scale Standard Deviation NA "NA" The standard deviation could not be calculated because only one participant was analyzed.	0.5 Score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline and Week 54

Population: The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. Tanner staging results for pubic hair were unavailable for the Metformin arm.

Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.

Outcome measures

Measure	Sitagliptin n=26 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=23 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=2 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males	0.5 Score on a scale Standard Deviation 0.7	0.6 Score on a scale Standard Deviation 0.5	—	0.5 Score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Week 20

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had dental data at baseline and Week 20.

Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 20 dental assessments versus baseline dental assessments.

Outcome measures

Measure	Sitagliptin n=88 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=85 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Participants With Worsening in Dental Status at Week 20 1. With ≥1 tooth with worsening in any category	32 Participants	25 Participants	1 Participants	0 Participants
Participants With Worsening in Dental Status at Week 20 2. With ≥1 tooth with worsening fracture	5 Participants	5 Participants	0 Participants	0 Participants
Participants With Worsening in Dental Status at Week 20 3. With ≥1 tooth with worsening discoloration	29 Participants	23 Participants	0 Participants	0 Participants
Participants With Worsening in Dental Status at Week 20 4. With ≥1 tooth with worsening enamel defect	7 Participants	4 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 54

Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had dental data at baseline and Week 54.

Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 54 dental assessments versus baseline dental assessments.

Outcome measures

Measure	Sitagliptin n=79 Participants Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Metformin n=78 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Metformin n=8 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.	Placebo/Sitagliptin n=5 Participants Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20.
Participants With Worsening in Dental Status at Week 54 1. With ≥1 tooth with worsening in any category	49 Participants	50 Participants	2 Participants	0 Participants
Participants With Worsening in Dental Status at Week 54 3. With ≥1 tooth with worsening discoloration	45 Participants	48 Participants	2 Participants	0 Participants
Participants With Worsening in Dental Status at Week 54 4. With ≥1 with worsening enamel defect	13 Participants	13 Participants	1 Participants	0 Participants
Participants With Worsening in Dental Status at Week 54 2. With ≥1 tooth with worsening fracture	13 Participants	15 Participants	1 Participants	0 Participants

Adverse Events

Sitagliptin

Serious events: 10 serious events

Other events: 62 other events

Deaths: 1 deaths

Placebo/Metformin

Serious events: 7 serious events

Other events: 53 other events

Deaths: 0 deaths

Metformin

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo/Sitagliptin

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sitagliptin n=95 participants at risk Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Metformin n=90 participants at risk Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Metformin n=9 participants at risk Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Sitagliptin n=5 participants at risk Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.
Gastrointestinal disorders Gastritis	1.1% 1/95 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Abscess soft tissue	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Appendicitis	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Dengue fever	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Gastroenteritis viral	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Pneumonia	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Injury, poisoning and procedural complications Concussion	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Investigations Blood glucose increased	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Metabolism and nutrition disorders Dehydration	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Metabolism and nutrition disorders Hyperglycaemia	3.2% 3/95 • Number of events 4 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Psychiatric disorders Affect lability	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Renal and urinary disorders Acute kidney injury	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Renal and urinary disorders Nephrolithiasis	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Reproductive system and breast disorders Ovarian cyst ruptured	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Skin and subcutaneous tissue disorders Erythema nodosum	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Social circumstances Sexual abuse	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.

Other adverse events

Measure	Sitagliptin n=95 participants at risk Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Metformin n=90 participants at risk Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Metformin n=9 participants at risk Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.	Placebo/Sitagliptin n=5 participants at risk Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.
Cardiac disorders Wandering pacemaker	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Eye disorders Blepharitis	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Eye disorders Eye pain	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Gastrointestinal disorders Abdominal pain	8.4% 8/95 • Number of events 10 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	7.8% 7/90 • Number of events 10 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Gastrointestinal disorders Diarrhoea	8.4% 8/95 • Number of events 9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	12.2% 11/90 • Number of events 14 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	22.2% 2/9 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Gastrointestinal disorders Dyspepsia	3.2% 3/95 • Number of events 6 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	2.2% 2/90 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Gastrointestinal disorders Nausea	5.3% 5/95 • Number of events 5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	4.4% 4/90 • Number of events 5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Gastrointestinal disorders Vomiting	6.3% 6/95 • Number of events 9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	7.8% 7/90 • Number of events 8 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
General disorders Influenza like illness	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 4 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
General disorders Pyrexia	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	6.7% 6/90 • Number of events 7 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Anal abscess	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Gastroenteritis	3.2% 3/95 • Number of events 4 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	7.8% 7/90 • Number of events 10 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Influenza	2.1% 2/95 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	6.7% 6/90 • Number of events 7 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Nasopharyngitis	15.8% 15/95 • Number of events 19 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	6.7% 6/90 • Number of events 6 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Pertussis	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Pharyngitis	6.3% 6/95 • Number of events 7 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	6.7% 6/90 • Number of events 6 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Upper respiratory tract infection	12.6% 12/95 • Number of events 15 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	13.3% 12/90 • Number of events 13 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Urinary tract infection	4.2% 4/95 • Number of events 4 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	10.0% 9/90 • Number of events 11 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Infections and infestations Viral infection	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 4 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Injury, poisoning and procedural complications Contusion	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Investigations Alanine aminotransferase increased	4.2% 4/95 • Number of events 4 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	3.3% 3/90 • Number of events 3 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Metabolism and nutrition disorders Hypoglycaemia	16.8% 16/95 • Number of events 107 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	13.3% 12/90 • Number of events 37 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	33.3% 3/9 • Number of events 65 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	40.0% 2/5 • Number of events 3 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Musculoskeletal and connective tissue disorders Back pain	3.2% 3/95 • Number of events 3 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Nervous system disorders Dizziness	3.2% 3/95 • Number of events 5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	2.2% 2/90 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	40.0% 2/5 • Number of events 4 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Nervous system disorders Headache	9.5% 9/95 • Number of events 9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	14.4% 13/90 • Number of events 16 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	22.2% 2/9 • Number of events 5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Renal and urinary disorders Dysuria	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Renal and urinary disorders Nephrolithiasis	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Reproductive system and breast disorders Dysmenorrhoea	2.1% 2/95 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Reproductive system and breast disorders Gynaecomastia	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.1% 2/95 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	2.2% 2/90 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.1% 1/95 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	1.1% 1/90 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/9 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	20.0% 1/5 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/95 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/90 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.
Vascular disorders Hypertension	2.1% 2/95 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	2.2% 2/90 • Number of events 2 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	11.1% 1/9 • Number of events 1 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.	0.00% 0/5 • SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/ presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
• Publication restrictions are in place

Restriction type: OTHER