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

Study Overview
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Brief Summary
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This study will assess the effect of sitagliptin/metformin FDC 50/1000 mg (Janumet®), MK-0431A) compared with the effect of glimepiride on hemoglobin A1c (HbA1c). The primary hypothesis is that after 30 weeks, sitagliptin/metformin FDC 50/1000 mg provides superior reduction in HbA1c (mean change from baseline) compared to glimepiride.

Official Title
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A Multicenter, Randomized, Double Blind Study to Compare the Efficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (Janumet®) Compared to Glimepiride in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin/Metformin FDC
* Drug: Comparator: Glimepiride
* Drug: Matching placebo to Sitagliptin/Metformin FDC
* Drug: Matching placebo to glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has type 2 diabetes mellitus Is currently not on an anti-hypoglycemic agent (AHA) (off for at least 12 weeks) and has a Visit 1/Screening Visit HbA1c greater than or equal to 7.0% and less than or equal to 9.5%; or is currently on AHA monotherapy or low-dose oral combination therapy (i.e., less than or equal to 50% maximum labeled dose of each agent) and has a Visit 1/Screening Visit HbA1c greater than or equal to 6.5% and less than or equal to 9.0% Exclusion Criteria: Has a history of type 1 diabetes mellitus or a history of ketoacidosis Has been on any investigational or approved glucagon-like peptide-1 (GLP-1) analogue (such as exenatide, liraglutide, etc.), any investigational or approved dipeptidyl peptidase IV (DPP-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, etc.) or a peroxisome proliferator-activated receptor (PPAR) gamma agonist agent (such as rosiglitazone, pioglitazone, etc.) within 12 weeks of Visit 1 Required insulin within the prior 12 weeks Has a hypersensitivity or contraindication to any sulfonylurea medication (such as glimepiride, glipizide, etc.), DPP-4 inhibitor (such as sitagliptin, vildagliptin, alogliptin, etc.), or biguanide medication (such as metformin, etc.) Has inadequately controlled hypertension Has cirrhosis or active liver disease Has severe cardiac conditions Is obese Has human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin/Metformin FDC<br>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. | Drug: Sitagliptin/Metformin FDC<br>* Sitagliptin phosphate plus metformin hydrochloride combination tablet (MK-0431A) orally up to 50/1000 mg BID for 30 weeks<br>* Other names: Janumet®;Drug: Matching placebo to glimepiride<br>* Matching placebo to glimepiride tablet orally daily for 30 weeks<br>|
| Active Comparator: Glimepiride<br>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. | Drug: Comparator: Glimepiride<br>* Glimepiride tablet orally up to 6 mg daily for 30 Weeks<br>* Other names: Amaryl®;Drug: Matching placebo to Sitagliptin/Metformin FDC<br>* Matching placebo to Sitagliptin/Metformin FDC 50/1000 mg orally BID for 30 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1C (HbA1C) at 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 (%). Change in A1C following 30 weeks of therapy (i.e., A1C at Week 30 minus A1C at baseline). | Baseline and Week 30 | 
| Number of Participants Who Experienced at Least One Adverse Event (AE) | 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. | Up to 32 weeks | 
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 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. | Up to 30 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30 | 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). | Baseline and Week 30 | 
| Percentage of Participants With One or More Episodes of Hypoglycemia | 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. | Up to Week 30 | 
| Change From Baseline in Body Weight at Week 30 | Change in body weight following 30 weeks of therapy (i.e., body weight at Week 30 minus body weight at baseline) | Baseline and Week 30 | 
| Percentage of Participants With HbA1C < 7.0% at 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 (%). | Week 30 |