Trial Outcomes & Findings for Safety and Efficacy of Co-Administration of Sitagliptin and Metformin in China (MK-0431-121) (NCT NCT01076088)

NCT ID: NCT01076088

Last Updated: 2017-05-23

Results Overview

A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 744 participants
• Primary outcome timeframe: Baseline and Week 24
• Results posted on: 2017-05-23

Participant Flow

In total, 744 participants were randomized to treatment. Of these 744 participants, 1 participant, assigned to the placebo group, did not receive study medication. This participant was not included in the safety analyses.

Participant milestones

Measure	Sitagliptin 50 mg + Metformin 500 mg Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg Metformin 500 mg twice daily	Metformin 850 Metformin 850 mg twice daily	Sitagliptin 100 mg Sitagliptin 100 mg once daily	Placebo Matching placebo to sitagliptin and/or metformin. Population includes 1 participant who did not receive any study medication.
Overall Study STARTED	122	125	126	124	120	127
Overall Study COMPLETED	111	107	109	109	104	104
Overall Study NOT COMPLETED	11	18	17	15	16	23

Reasons for withdrawal

Measure	Sitagliptin 50 mg + Metformin 500 mg Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg Metformin 500 mg twice daily	Metformin 850 Metformin 850 mg twice daily	Sitagliptin 100 mg Sitagliptin 100 mg once daily	Placebo Matching placebo to sitagliptin and/or metformin. Population includes 1 participant who did not receive any study medication.
Overall Study Adverse Event	1	6	3	2	3	3
Overall Study Lost to Follow-up	1	1	0	1	1	2
Overall Study Non-compliance with study drug	0	0	0	1	0	0
Overall Study Physician Decision	1	3	0	1	1	0
Overall Study Withdrawal by Subject	8	8	14	10	11	17
Overall Study Other protocol specified criteria	0	0	0	0	0	1

Baseline Characteristics

Safety and Efficacy of Co-Administration of Sitagliptin and Metformin in China (MK-0431-121)

Baseline characteristics by cohort

Measure	Sitagliptin 50 mg + Metformin 500 mg n=122 Participants Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg n=125 Participants Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg n=126 Participants Metformin 500 mg twice daily	Metformin 850 n=124 Participants Metformin 850 mg twice daily	Sitagliptin 100 mg n=120 Participants Sitagliptin 100 mg once daily	Placebo n=127 Participants Matching placebo to sitagliptin and/or metformin. Population includes 1 participant who did not receive any study medication.	Total n=744 Participants Total of all reporting groups
Age, Continuous	52.6 Years STANDARD_DEVIATION 11.3 • n=5 Participants	52.4 Years STANDARD_DEVIATION 9.3 • n=7 Participants	52.6 Years STANDARD_DEVIATION 9.5 • n=5 Participants	53.0 Years STANDARD_DEVIATION 10.3 • n=4 Participants	51.7 Years STANDARD_DEVIATION 10.2 • n=21 Participants	53.6 Years STANDARD_DEVIATION 9.7 • n=8 Participants	52.7 Years STANDARD_DEVIATION 10.0 • n=8 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	58 Participants n=7 Participants	57 Participants n=5 Participants	49 Participants n=4 Participants	46 Participants n=21 Participants	40 Participants n=8 Participants	287 Participants n=8 Participants
Sex: Female, Male Male	85 Participants n=5 Participants	67 Participants n=7 Participants	69 Participants n=5 Participants	75 Participants n=4 Participants	74 Participants n=21 Participants	87 Participants n=8 Participants	457 Participants n=8 Participants
Hemoglobin A1c (A1C)	8.46 Percent of glycosylated hemoglobin STANDARD_DEVIATION 0.97 • n=5 Participants	8.66 Percent of glycosylated hemoglobin STANDARD_DEVIATION 0.95 • n=7 Participants	8.69 Percent of glycosylated hemoglobin STANDARD_DEVIATION 0.99 • n=5 Participants	8.67 Percent of glycosylated hemoglobin STANDARD_DEVIATION 1.08 • n=4 Participants	8.74 Percent of glycosylated hemoglobin STANDARD_DEVIATION 1.14 • n=21 Participants	8.97 Percent of glycosylated hemoglobin STANDARD_DEVIATION 1.05 • n=8 Participants	8.70 Percent of glycosylated hemoglobin STANDARD_DEVIATION 1.04 • n=8 Participants
Fasting plasma glucose (FPG)	175.6 mg/dL STANDARD_DEVIATION 40.6 • n=5 Participants	181.9 mg/dL STANDARD_DEVIATION 43.0 • n=7 Participants	184.6 mg/dL STANDARD_DEVIATION 46.8 • n=5 Participants	183.5 mg/dL STANDARD_DEVIATION 47.7 • n=4 Participants	182.5 mg/dL STANDARD_DEVIATION 44.0 • n=21 Participants	185.8 mg/dL STANDARD_DEVIATION 47.3 • n=8 Participants	182.3 mg/dL STANDARD_DEVIATION 45.0 • n=8 Participants
2-hour post meal glucose (2-h PMG)	292.7 mg/dL STANDARD_DEVIATION 81.2 • n=5 Participants	292.9 mg/dL STANDARD_DEVIATION 68.4 • n=7 Participants	303.2 mg/dL STANDARD_DEVIATION 74.1 • n=5 Participants	298.8 mg/dL STANDARD_DEVIATION 74.6 • n=4 Participants	297.7 mg/dL STANDARD_DEVIATION 74.7 • n=21 Participants	308.3 mg/dL STANDARD_DEVIATION 83.6 • n=8 Participants	299.0 mg/dL STANDARD_DEVIATION 76.2 • n=8 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for the A1C subsequent to at least 1 dose of study treatment, or lacked baseline data for the A1C. Last observation carried forward (missing data approach).

A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.

Outcome measures

Measure	Sitagliptin 50 mg + Metformin 500 mg n=118 Participants Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg n=114 Participants Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg n=116 Participants Metformin 500 mg twice daily	Metformin 850 mg n=117 Participants Metformin 850 mg twice daily	Sitagliptin 100 mg n=113 Participants Sitagliptin 100 mg once daily	Placebo n=117 Participants Matching placebo to sitagliptin and/or metformin
Change From Baseline in Hemoglobin A1C (A1C) at Week 24	-1.67 Percent of glycosylated hemoglobin Interval -1.92 to -1.43	-1.83 Percent of glycosylated hemoglobin Interval -2.07 to -1.58	-1.29 Percent of glycosylated hemoglobin Interval -1.54 to -1.04	-1.56 Percent of glycosylated hemoglobin Interval -1.8 to -1.32	-0.99 Percent of glycosylated hemoglobin Interval -1.24 to -0.75	-0.59 Percent of glycosylated hemoglobin Interval -0.84 to -0.34

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for 2-h PMG subsequent to at least 1 dose of study treatment, or lacked baseline data for 2-h PMG. Last observation carried forward (missing data approach).

Change from baseline in 2-h PMG at Week 24 is defined as Week 24 2-h PMG minus Week 0 2-h PMG.

Outcome measures

Measure	Sitagliptin 50 mg + Metformin 500 mg n=110 Participants Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg n=110 Participants Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg n=112 Participants Metformin 500 mg twice daily	Metformin 850 mg n=108 Participants Metformin 850 mg twice daily	Sitagliptin 100 mg n=107 Participants Sitagliptin 100 mg once daily	Placebo n=107 Participants Matching placebo to sitagliptin and/or metformin
Change From Baseline in 2-hour Post Meal Glucose (2-h PMG) at Week 24	-97.05 mg/dL Interval -109.01 to -85.09	-109.46 mg/dL Interval -121.47 to -97.44	-65.67 mg/dL Interval -77.76 to -53.58	-90.93 mg/dL Interval -103.04 to -78.83	-48.11 mg/dL Interval -60.37 to -35.85	-21.88 mg/dL Interval -34.33 to -9.43

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for FPG subsequent to at least 1 dose of study treatment, or lacked baseline data for FPG. Last observation carried forward (missing data approach).

Change from baseline in FPG at Week 24 is defined as Week 24 FPG minus Week 0 FPG.

Outcome measures

Measure	Sitagliptin 50 mg + Metformin 500 mg n=118 Participants Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg n=116 Participants Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg n=119 Participants Metformin 500 mg twice daily	Metformin 850 mg n=119 Participants Metformin 850 mg twice daily	Sitagliptin 100 mg n=114 Participants Sitagliptin 100 mg once daily	Placebo n=119 Participants Matching placebo to sitagliptin and/or metformin
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	-39.38 mg/dL Interval -46.29 to -32.47	-47.74 mg/dL Interval -54.73 to -40.75	-33.66 mg/dL Interval -40.66 to -26.66	-39.63 mg/dL Interval -46.5 to -32.76	-21.86 mg/dL Interval -28.92 to -14.8	-11.93 mg/dL Interval -18.94 to -4.92

Adverse Events

Sitagliptin 50 mg + Metformin 500 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Sitagliptin 50 mg + Metformin 850 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Metformin 500 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Metformin 850

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Sitagliptin 100 mg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sitagliptin 50 mg + Metformin 500 mg n=122 participants at risk Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg n=125 participants at risk Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg n=126 participants at risk Metformin 500 mg twice daily	Metformin 850 n=124 participants at risk Metformin 850 mg twice daily	Sitagliptin 100 mg n=120 participants at risk Sitagliptin 100 mg once daily	Placebo n=126 participants at risk Matching placebo to sitagliptin and/or metformin. Population excludes 1 participant who did not receive any study medication.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.81% 1/124 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.81% 1/124 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Investigations Coagulation time shortened	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/124 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.83% 1/120 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Investigations Transaminases increased	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/124 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.83% 1/120 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/124 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.79% 1/126 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Nervous system disorders Cerebral infarction	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/124 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.83% 1/120 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.81% 1/124 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Infections and infestations Lung infection	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/124 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.79% 1/126 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/124 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.79% 1/126 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/122 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/125 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.79% 1/126 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/124 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.

Other adverse events

Measure	Sitagliptin 50 mg + Metformin 500 mg n=122 participants at risk Sitagliptin 50 mg twice daily + metformin 500 mg twice daily	Sitagliptin 50 mg + Metformin 850 mg n=125 participants at risk Sitagliptin 50 mg twice daily + metformin 850 mg twice daily	Metformin 500 mg n=126 participants at risk Metformin 500 mg twice daily	Metformin 850 n=124 participants at risk Metformin 850 mg twice daily	Sitagliptin 100 mg n=120 participants at risk Sitagliptin 100 mg once daily	Placebo n=126 participants at risk Matching placebo to sitagliptin and/or metformin. Population excludes 1 participant who did not receive any study medication.
Gastrointestinal disorders Diarrhoea	2.5% 3/122 • Number of events 3 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	3.2% 4/125 • Number of events 5 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	3.2% 4/126 • Number of events 4 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	7.3% 9/124 • Number of events 10 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	1.7% 2/120 • Number of events 3 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	3.2% 4/126 • Number of events 4 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Gastrointestinal disorders Nausea	1.6% 2/122 • Number of events 2 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	6.4% 8/125 • Number of events 10 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.79% 1/126 • Number of events 1 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	3.2% 4/124 • Number of events 4 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/120 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	0.00% 0/126 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.
Metabolism and nutrition disorders Hypoglycaemia	3.3% 4/122 • Number of events 4 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	5.6% 7/125 • Number of events 11 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	2.4% 3/126 • Number of events 3 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	1.6% 2/124 • Number of events 2 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	3.3% 4/120 • Number of events 7 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.	1.6% 2/126 • Number of events 2 All participants as treated population. Serious and non-serious adverse events (AEs) include and exclude data after rescue therapy, respectively. One event of hypoglycaemia that, per protocol, should have been reported as an AE was not reported as an AE. This event occurred in a participant who had another event of hypoglycaemia that was reported.

Additional Information

Senior Vice President,Global Clinical Development

Merck Sharp & Dohme Corp.

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.
• Publication restrictions are in place

Restriction type: OTHER