Trial Outcomes & Findings for Efficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (FDC) Compared to Glimepiride in Participants With Type 2 Diabetes Mellitus (MK-0431A-202) (NCT NCT00993187)

Last Updated: 2018-08-22

Results Overview

HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Change in A1C following 30 weeks of therapy (i.e., A1C at Week 30 minus A1C at baseline).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

292 participants

Primary outcome timeframe

Baseline and Week 30

Results posted on

2018-08-22

Participant Flow

Participant milestones

Participant milestones
Measure	Sitagliptin/Metformin Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Overall Study STARTED	147	145
Overall Study Received at Least 1 Dose of Study Drug	146	144
Overall Study COMPLETED	121	108
Overall Study NOT COMPLETED	26	37

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (FDC) Compared to Glimepiride in Participants With Type 2 Diabetes Mellitus (MK-0431A-202)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin/Metformin n=147 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=145 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.	Total n=292 Participants Total of all reporting groups
Age, Continuous	54.8 Years STANDARD_DEVIATION 8.5 • n=5 Participants	53.1 Years STANDARD_DEVIATION 9.2 • n=7 Participants	53.9 Years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	61 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	84 Participants n=7 Participants	165 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 30

Population: Full-Analysis-Set (FAS) Population included all randomized participants who had a baseline measurement, consumed at least one dose of study medication, and had at least one post-randomization measurement.

Outcome measures

Outcome measures
Measure	Sitagliptin/Metformin n=138 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=137 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30	-1.5 Percent of total hemoglobin Interval -1.6 to -1.4	-0.7 Percent of total hemoglobin Interval -0.8 to -0.6

PRIMARY outcome

Timeframe: Up to 32 weeks

Population: The All Patients as Treated (APaT) Population includes all randomized participants who received at least 1 dose of study medication.

An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

Outcome measures

Outcome measures
Measure	Sitagliptin/Metformin n=146 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=144 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Number of Participants Who Experienced at Least One Adverse Event (AE)	88 Participants	101 Participants

PRIMARY outcome

Timeframe: Up to 30 weeks

Population: The APaT Population includes all randomized participants who received at least 1 dose of study medication.

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

Outcome measures

Outcome measures
Measure	Sitagliptin/Metformin n=146 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=144 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event	8 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline and Week 30

Population: The FAS Population included all randomized participants who had a baseline measurement, consumed at least one dose of study medication, and had at least one post-randomization measurement.

Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 30 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 30 minus FPG at baseline).

Outcome measures

Outcome measures
Measure	Sitagliptin/Metformin n=138 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=137 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30	-47.0 mg/dL Interval -51.7 to -42.3	-23.5 mg/dL Interval -28.2 to -18.8

SECONDARY outcome

Timeframe: Up to Week 30

Population: The APaT Population includes all randomized participants who received at least 1 dose of study medication.

Symptomatic episodes assessed as likely to be due to hypoglycemia were reported by investigators as adverse experiences of hypoglycemia. Adverse experiences of hypoglycemia were based on all reports of hypoglycemia; a concurrent glucose measurement was not required.

Outcome measures

Outcome measures
Measure	Sitagliptin/Metformin n=146 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=144 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Percentage of Participants With One or More Episodes of Hypoglycemia	5.5 Percentage of participants	20.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 30

Population: The APaT Population includes all randomized participants who received at least 1 dose of study medication.

Change in body weight following 30 weeks of therapy (i.e., body weight at Week 30 minus body weight at baseline)

Outcome measures

Outcome measures
Measure	Sitagliptin/Metformin n=146 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=144 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Change From Baseline in Body Weight at Week 30	-0.83 kg 95% Confidence Interval 1.8 • Interval -1.16 to -0.49	0.90 kg 95% Confidence Interval 2.4 • Interval 0.56 to 1.23

SECONDARY outcome

Timeframe: Week 30

HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%).

Outcome measures

Outcome measures
Measure	Sitagliptin/Metformin n=138 Participants Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=137 Participants Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Percentage of Participants With HbA1C < 7.0% at Week 30	81.2 Percentage of Participants	40.1 Percentage of Participants

Adverse Events

Sitagliptin/Metformin

Serious events: 8 serious events

Other events: 62 other events

Deaths: 0 deaths

Glimepiride

Serious events: 9 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sitagliptin/Metformin n=146 participants at risk Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=144 participants at risk Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Gastrointestinal disorders DIARRHOEA	10.3% 15/146 • Number of events 22 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	2.8% 4/144 • Number of events 4 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders DYSPEPSIA	13.0% 19/146 • Number of events 20 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	6.2% 9/144 • Number of events 10 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders NAUSEA	6.8% 10/146 • Number of events 12 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	2.8% 4/144 • Number of events 4 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Infections and infestations NASOPHARYNGITIS	8.9% 13/146 • Number of events 19 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	11.8% 17/144 • Number of events 22 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	8.2% 12/146 • Number of events 13 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	2.8% 4/144 • Number of events 4 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Metabolism and nutrition disorders HYPOGLYCAEMIA	5.5% 8/146 • Number of events 12 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	20.1% 29/144 • Number of events 53 • Up to 32 weeks The APaT Population includes 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

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

Measure	Sitagliptin/Metformin n=146 participants at risk Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Glimepiride n=144 participants at risk Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.
Gastrointestinal disorders DUODENAL ULCER HAEMORRHAGE	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders PANCREATITIS ACUTE	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Infections and infestations ENTEROCOLITIS INFECTIOUS	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Infections and infestations HERPES ZOSTER	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Infections and infestations INFECTIVE SPONDYLITIS	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Infections and infestations INFLUENZA	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications CARTILAGE INJURY	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications CONTUSION	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications OVERDOSE	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Metabolism and nutrition disorders HYPERGLYCAEMIA	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders GOUTY ARTHRITIS	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders SPONDYLOLISTHESIS	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PAPILLARY THYROID CANCER	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) THYROID CANCER	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) UTERINE LEIOMYOMA	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Nervous system disorders INTRACRANIAL ANEURYSM	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Nervous system disorders SYNCOPE	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Renal and urinary disorders URINARY INCONTINENCE	0.00% 0/146 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.69% 1/144 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders URTICARIA	0.68% 1/146 • Number of events 1 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.	0.00% 0/144 • Up to 32 weeks The APaT Population includes all randomized participants who received at least 1 dose of study medication.