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

• β-cell Sensitivity [ Time Frame: 6 hour post-dose (4 hour postmeal) on Day 2 ] [ Designated as safety issue: No ]
  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.
• Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations [ Time Frame: 6 hours postdose (4 hours postmeal) on Day 2 ] [ Designated as safety issue: No ]
  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.

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.

• Drug: sitagliptin phosphate
  Sitagliptin 100 mg tablet on Day 1 and Day 2 in the morning. There will be a 7-day washout between treatment periods.
  Other Name: Januvia
• Drug: metformin hydrochloride
  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.
  Other Name: Glucophage
• Drug: Comparator: placebo sitagliptin
  Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods.
• Drug: Comparator: placebo metformin
  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.

• Experimental: Sitagliptin + placebo metformin
  Interventions:

  • Drug: sitagliptin phosphate
  • Drug: Comparator: placebo metformin
• Experimental: Metformin + placebo sitagliptin
  Interventions:

  • Drug: metformin hydrochloride
  • Drug: Comparator: placebo sitagliptin
• Experimental: Sitagliptin + metformin
  Co-administration of sitagliptin and metformin
  Interventions:

  • Drug: sitagliptin phosphate
  • Drug: metformin hydrochloride
• Placebo Comparator: Placebo sitagliptin + placebo metformin
  Co-administration of placebo to sitagliptin and placebo to metformin
  Interventions:

  • Drug: Comparator: placebo sitagliptin
  • Drug: Comparator: placebo metformin

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