Trial Outcomes & Findings for A Study of the Safety and Efficacy of Sitagliptin Addition During Metformin Up-titration (MK-0431-848) (NCT NCT02791490)

Last Updated: 2019-02-28

Results Overview

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. The change from baseline represents the Week 20 A1C value minus the Week 0 (baseline) A1C value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

458 participants

Primary outcome timeframe

Baseline and Week 20

Results posted on

2019-02-28

Participant Flow

Participant milestones

Participant milestones
Measure	Sitagliptin Participants received sitagliptin 100 mg once daily for 20 weeks. They also received immediate-release metformin (Met-IR), which was titrated from a baseline dose of 1000 mg/day (500 mg/twice a day \[b.i.d\]) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Overall Study STARTED	229	229
Overall Study COMPLETED	226	221
Overall Study NOT COMPLETED	3	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin Participants received sitagliptin 100 mg once daily for 20 weeks. They also received immediate-release metformin (Met-IR), which was titrated from a baseline dose of 1000 mg/day (500 mg/twice a day \[b.i.d\]) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Overall Study Lost to Follow-up	1	2
Overall Study Withdrawal by Subject	2	6

Baseline Characteristics

A Study of the Safety and Efficacy of Sitagliptin Addition During Metformin Up-titration (MK-0431-848)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=229 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Total n=458 Participants Total of all reporting groups
Age, Continuous	55.6 Years STANDARD_DEVIATION 10.5 • n=5 Participants	55.3 Years STANDARD_DEVIATION 10.4 • n=7 Participants	55.5 Years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	139 Participants n=5 Participants	136 Participants n=7 Participants	275 Participants n=5 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	93 Participants n=7 Participants	183 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	147 Participants n=5 Participants	151 Participants n=7 Participants	298 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=5 Participants	70 Participants n=7 Participants	148 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	23 Participants n=5 Participants	27 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	167 Participants n=5 Participants	155 Participants n=7 Participants	322 Participants n=5 Participants
Race (NIH/OMB) More than one race	31 Participants n=5 Participants	39 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Hemoglobin A1C (%)	8.6 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	8.7 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.0 • n=7 Participants	8.7 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants
Fasting Plasma Glucose	181.7 mg/dL STANDARD_DEVIATION 41.6 • n=5 Participants	184.4 mg/dL STANDARD_DEVIATION 44.7 • n=7 Participants	183.0 mg/dL STANDARD_DEVIATION 43.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 20

Population: All randomized participants who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint

Outcome measures

Outcome measures
Measure	Sitagliptin n=229 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Change From Baseline in Hemoglobin A1C at Week 20	-1.10 A1C (%) Interval -1.28 to -0.93	-0.69 A1C (%) Interval -0.88 to -0.51

PRIMARY outcome

Timeframe: Up to 22 weeks

Population: All randomized participants who received at least 1 dose of study medication

An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Outcome measures

Outcome measures
Measure	Sitagliptin n=229 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Percentage of Participants Who Experienced at Least One Adverse Event (AE)	44.1 Percentage of participants	45.9 Percentage of participants

PRIMARY outcome

Timeframe: Up to 20 weeks

Population: All randomized participants who received at least 1 dose of study medication

Outcome measures

Outcome measures
Measure	Sitagliptin n=229 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event	0.9 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 20

Population: All randomized participants who received at least 1 dose of study treatment and had at least 1 observation for the analysis endpoint

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.

Outcome measures

Outcome measures
Measure	Sitagliptin n=229 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Percentage of Participants With Hemoglobin A1C <7% at Week 20	28.8 Percentage of participants	16.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: All randomized participants who received at least 1 dose of study treatment and had at least 1 observation for the analysis endpoint

Plasma glucose was measured on a fasting basis and is expressed as mg/dL. Blood was drawn predose on Day 1 and after 20 weeks of treatment to determine change in FPG levels. The change from baseline represents the Week 20 FPG value minus the Week 0 (baseline) FPG value.

Outcome measures

Outcome measures
Measure	Sitagliptin n=229 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20	-29.3 mg/dL Interval -37.5 to -21.1	-16.9 mg/dL Interval -25.2 to -8.6

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: The subgroup of randomized participants who had a baseline hemoglobin A1C ≥8.5%, received at least 1 dose of study medication, and had at least 1 observation for the analysis endpoint

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.

Outcome measures

Outcome measures
Measure	Sitagliptin n=122 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=122 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Percentage of Participants With Hemoglobin A1C ≥8.5% at Baseline That Attained A1C Goal of <7% at Week 20	15.6 Percentage of participants	5.7 Percentage of participants

SECONDARY outcome

Timeframe: Up to 20 weeks

Population: All randomized participants who received at least 1 dose of study treatment

Participants who met pre-specified criteria for glycemic rescue received appropriate rescue therapy. The choice of anti-hyperglycemic rescue agent, dose, and regimen was directed by the investigator, as clinically appropriate.

Outcome measures

Outcome measures
Measure	Sitagliptin n=229 Participants Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 Participants Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Percentage of Participants Receiving Glycemic Rescue Therapy	1.3 Percentage of participants	3.1 Percentage of participants

Adverse Events

Sitagliptin

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin n=229 participants at risk Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 participants at risk Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Cardiac disorders Acute myocardial infarction	0.44% 1/229 • Number of events 1 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication
Cardiac disorders Myocardial ischaemia	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.44% 1/229 • Number of events 1 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication
Hepatobiliary disorders Fatty liver alcoholic	0.44% 1/229 • Number of events 1 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication
Injury, poisoning and procedural complications Stab wound	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.44% 1/229 • Number of events 1 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.44% 1/229 • Number of events 1 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication
Renal and urinary disorders Acute kidney injury	0.44% 1/229 • Number of events 1 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication
Reproductive system and breast disorders Metrorrhagia	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.44% 1/229 • Number of events 1 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication
Reproductive system and breast disorders Prostatitis	0.44% 1/229 • Number of events 2 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	0.00% 0/229 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication

Other adverse events

Other adverse events
Measure	Sitagliptin n=229 participants at risk Participants received sitagliptin 100 mg once daily for 20 weeks. They also received Met-IR, which was titrated from a baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.	Placebo n=229 participants at risk Participants received placebo matching sitagliptin once daily for 20 weeks. They also received Met-IR, which was titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants also received glycemic rescue therapy as needed.
Gastrointestinal disorders Diarrhoea	7.9% 18/229 • Number of events 18 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication	4.8% 11/229 • Number of events 11 • Up to 22 weeks All randomized participants who received at least 1 dose of study medication

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

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 trial 45 days prior to submission for publication/presentation. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER