A Study of the Effects of Co-Administration of Sitagliptin (MK-0431) and Metformin on Incretin Hormone Concentrations (MK-0431-110)

Study Overview
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Brief Summary
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This study will assess the effects of sitagliptin and metformin alone and after co-administration on incretin hormone concentrations in patients with Type 2 diabetes.

Official Title
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A Study to Assess the Effects of Co-Administration of Sitagliptin and Metformin on Incretin Hormone Concentrations

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: sitagliptin phosphate
* Drug: metformin hydrochloride
* Drug: Comparator: placebo sitagliptin
* Drug: Comparator: placebo metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects must have a negative pregnancy test Subject has type 2 diabetes and is not currently receiving treatment with an oral AHA agent, has not received such treatment for 3 months prior to study, and/or has not received more than 4 total weeks treatment with an oral AHA agent for 12 to 18 months prior to the study Subject is a nonsmoker or has not smoked and/or used nicotine for at least 6 months Exclusion Criteria: Subject has a history of stroke, seizures, or major neurological disorders Female subject is breastfeeding Subject cannot refrain from use of any prescription or non-prescription drugs beginning 2 weeks prior to first dose of study drug Subject consumes more than 3 alcoholic beverages per day Subject consumes more than 6 caffeinated beverages per day Subject has had major surgery, or has donated or lost 1 unit of blood within 4 weeks of screening Subject has a history of cancer, except certain skin or cervical cancer or other cancers treated more than 10 years prior to screening Subject has a history of multiple and/or severe allergies or intolerance to drugs or food

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin + placebo metformin<br> | Drug: sitagliptin phosphate<br>* Sitagliptin 100 mg tablet on Day 1 and Day 2 in the morning. There will be a 7-day washout between treatment periods.<br>* Other names: Januvia;Drug: Comparator: placebo metformin<br>* Placebo to metformin 500 mg tablet in the morning and evening on Day 1 and two placebo to metformin 500 mg tablets (1000 mg total dose) in the morning of Day 2. There will be a 7-day wash out between treatment periods.<br>|
| Experimental: Metformin + placebo sitagliptin<br> | Drug: metformin hydrochloride<br>* Metformin 500 mg tablet in the morning and evening on Day 1 and two 500 mg tablets of metformin (total dose 1000 mg) on Day 2 in the morning. There will be a 7-day washout between treatment periods.<br>* Other names: Glucophage;Drug: Comparator: placebo sitagliptin<br>* Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods.<br>|
| Experimental: Sitagliptin + metformin<br>Co-administration of sitagliptin and metformin | Drug: sitagliptin phosphate<br>* Sitagliptin 100 mg tablet on Day 1 and Day 2 in the morning. There will be a 7-day washout between treatment periods.<br>* Other names: Januvia;Drug: metformin hydrochloride<br>* Metformin 500 mg tablet in the morning and evening on Day 1 and two 500 mg tablets of metformin (total dose 1000 mg) on Day 2 in the morning. There will be a 7-day washout between treatment periods.<br>* Other names: Glucophage;|
| Placebo Comparator: Placebo sitagliptin + placebo metformin<br>Co-administration of placebo to sitagliptin and placebo to metformin | Drug: Comparator: placebo sitagliptin<br>* Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods.<br>Drug: Comparator: placebo metformin<br>* Placebo to metformin 500 mg tablet in the morning and evening on Day 1 and two placebo to metformin 500 mg tablets (1000 mg total dose) in the morning of Day 2. There will be a 7-day wash out between treatment periods.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental Post-prandial 4-hour Weighted Mean Active Glucagon-like Peptide-1 (GLP-1) Plasma Concentrations | Meal was given 2 hours postdose. Blood samples for determination of active GLP-1 concentration were collected (4 hours postmeal) on Day 2 in each treatment period. | 6 hours postdose (4 hours postmeal) on Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| β-cell Sensitivity | β-cell sensitivity was defined as the incremental post-prandial 4-hour area under the curve (AUC) for insulin secretion rate (ISR) normalized by the incremental post-prandial 4-hour plasma glucose AUC. | 6 hour post-dose (4 hour postmeal) on Day 2 | 
| Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations | Meal was given 2 hours postdose. Blood samples for determination of glucose concentration were collected (4 hours postmeal) on Day 2 in each treatment period. | 6 hours postdose (4 hours postmeal) on Day 2 |