A Study to Evaluate the Safety and Efficacy of Sitagliptin 100 mg in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control (MK-0431-229)

• Change From Baseline in Hemoglobin A1C (%) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  Change from baseline reflects the Week 24 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.
• Number of Participants With One or More Adverse Events (AEs) - Week 0 to Week 54 [ Time Frame: Week 0 to Week 54 ] [ Designated as safety issue: Yes ]
• Number of Participants Discontinuing Study Drug Due to An Adverse Event [ Time Frame: Week 0 to Week 54 ] [ Designated as safety issue: Yes ]

• Change From Baseline in 2-hour Post-Meal Glucose at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  Change from baseline reflects the Week 24 value minus the baseline value. Two-hour post-meal glucose was measured following a standard meal.
• Change From Baseline in Fasting Plasma Glucose at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  Change from baseline reflects the Week 24 value minus the baseline value.

• Change from baseline in 2-hour post-meal glucose (PMG)(following a standard meal), compared with the addition of placebo [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
• A change in fasting plasma glucose (FPG) (compared with the addition of placebo, in patients who are taking glimepiride or gliclazide and metformin) [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]

This study will evaluate whether the addition of Sitagliptin treatment provides a greater decrease in A1C levels compared to placebo in participants with inadequate glycemic control on sulfonylurea and metformin combination therapy.

• Drug: Sitagliptin phosphate
  Phase A (Weeks 0-24): Sitagliptin 100 mg once a day for 24 weeks; Phase B (Weeks 24-54): Sitagliptin 100 mg once a day for 30 weeks
  Other Name: Januvia
• Drug: Comparator: placebo to pioglitazone
  Phase B (Weeks 24-54): placebo to pioglitazone 30 mg once a day for 30 weeks
• Drug: Comparator: placebo to Sitagliptin
  Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg once a day for 24 weeks; Phase B (Weeks 24-54): placebo to Sitagliptin once a day for 30 weeks
• Drug: Comparator: pioglitazone
  Phase B (Weeks 24-54): pioglitazone 30 mg once a day for 30 weeks
  Other Name: Actos;
• Drug: Glimepiride or gliclazide
  Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of glimepiride or gliclazide; Phase B (Weeks 24-54): stable dose, as prescribed by investigator, of glimepiride or gliclazide
• Drug: Metformin
  Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of metformin; Phase B (Weeks 24- 54): stable dose, as prescribed by investigator, of metformin
• Drug: Pioglitazone rescue therapy
  Phase A (Weeks 0-24): participants not meeting specific glycemic goals will receive pioglitazone (open label) at a dose determined by the investigator. These participants will not initiate Phase B (Weeks 24-54) double blind pioglitazone.
  Other Name: Actos

• Active Comparator: placebo/pioglitazone
  Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): placebo to Sitagliptin 100 mg + pioglitazone 30 mg
  Interventions:

  • Drug: Comparator: placebo to Sitagliptin
  • Drug: Comparator: pioglitazone
  • Drug: Glimepiride or gliclazide
  • Drug: Metformin
  • Drug: Pioglitazone rescue therapy
• Experimental: Sitagliptin
  Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + placebo to pioglitazone
  Interventions:

  • Drug: Sitagliptin phosphate
  • Drug: Comparator: placebo to pioglitazone
  • Drug: Glimepiride or gliclazide
  • Drug: Metformin
  • Drug: Pioglitazone rescue therapy

Inclusion Criteria:

• Type 2 diabetes mellitus
• Hemoglobin A1C of ≥7.5% and ≤10.5%
• Currently taking a stable dose of metformin (at least 1500 mg/day) and either glimepiride (at least 2 mg/day) or gliclazide (at least 50% of maximum registered dose) for at least 10 weeks prior to study start
• Male, or a female who is highly unlikely to conceive

Exclusion Criteria:

• Type 1 diabetes mellitus or ketoacidosis
• Taking a dipeptidyl peptidase-4 (DPP-4) inhibitor (such as sitagliptin) or a glucagon-like peptide-1 (GLP-1) mimetic (such as exenatide or liraglutide) or required insulin therapy within 12 weeks prior to study start
• On a weight loss program not in the maintenance phase or on a weight loss medication
• History of liver disease, heart failure, heart disease, stroke, high blood pressure, blood disorders, or cancer
• HIV positive
• Pregnant