Study to Assess Safety & Efficacy of Sitagliptin as Initial Monotherapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants (MK-0431-083 AM1)

• Change from baseline in A1C [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
• Number of participants with adverse events [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]

The purpose of the study is to assess the safety of the addition of sitagliptin, and its effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control.

• Diabetes Mellitus
• Type 2 Diabetes

• Drug: Sitagliptin
  100 mg oral tablet of sitagliptin prior to the morning meal
  Other Name: Januvia
• Drug: Metformin
  Metformin(500 mg) oral tablets prior to both the morning and evening meals
  Other Name: Glucophage
• Drug: Placebo to sitagliptin

  Placebo run-in: For 1 week all participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal and 2 oral tablets of placebo to metformin prior to both the morning and evening meals.

  After randomization: Participants randomized to the metformin arm and the 2 arms with placebo for phase A will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.

  Phase B: Participants in the metformin arm and the placebo phase A/ metformin phase B arm will continue to receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.

• Drug: Placebo to metformin

  Placebo run-in: For 1 week all participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal and 2 oral tablets of placebo to metformin prior to both the morning and evening meals.

  After randomization: Participants randomized to the sitagliptin arm and the 2 arms with placebo for phase A will receive 2 oral tablets of placebo to metformin prior to both the morning and evening meal

  Phase B:

  Participants in the sitagliptin arm and the placebo phase A/ sitagliptin phase B arm will continue to receive 2 oral tablets of placebo to metformin prior to both the morning and evening meal

• Experimental: Sitagliptin
  Sitagliptin 100 mg oral tablet once a day and placebo to metformin oral tablet twice a day for 54 weeks
  Interventions:

  • Drug: Sitagliptin
  • Drug: Placebo to sitagliptin
  • Drug: Placebo to metformin
• Active Comparator: Metformin
  Metformin (500 mg) oral tablets, twice a day and placebo to sitagliptin (100 mg), oral tablet once a day for 54 weeks
  Interventions:

  • Drug: Metformin
  • Drug: Placebo to sitagliptin
  • Drug: Placebo to metformin
• Experimental: Placebo phase A / Metformin phase B
  Placebo to sitagliptin oral tablet once a day and placebo to metformin oral tablets twice a day for 16 weeks (Phase A), followed by metformin oral tablets twice a day and placebo to sitagliptin oral tablet once a day for 38 weeks (Phase B).
  Interventions:

  • Drug: Metformin
  • Drug: Placebo to sitagliptin
  • Drug: Placebo to metformin
• Experimental: Placebo phase A / Sitagliptin phase B
  Placebo to sitagliptin oral tablet once a day and placebo to metformin oral tablets twice a day for 16 weeks (Phase A), followed by sitagliptin oral tablet once a day and placebo to metformin oral tablets twice a day for 38 weeks (Phase B).
  Interventions:

  • Drug: Sitagliptin
  • Drug: Placebo to sitagliptin
  • Drug: Placebo to metformin

Inclusion Criteria:

• Type 2 Diabetes Mellitus (T2DM)
• Has not received treatment with an oral antihyperglycemic agent (AHA) for ≥12 weeks prior to the Screening Visit/Visit 1, or with insulin for at least 6 months prior to the Screening Visit/Visit 1.
• An A1C of ≥7.0% and ≤10.0%.

Exclusion Criteria:

• Diabetes for >1 year.
• History of type 1 diabetes mellitus, autoimmune diabetes mellitus or has a positive antibody screen for anti-GAD (Glutamic Acid Decarboxylase) or (Islet cell autoantigen)ICA-512.
• Known monogenic diabetes, secondary diabetes, or a genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
• Symptomatic hyperglycemia and/or moderate to large ketonuria requiring immediate initiation of antihyperglycemic therapy.
• Previously taken a DPP-4 (Dipeptidyl peptidase-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or (Glucagon-like peptide-1) GLP-1 receptor agonist (such as exenatide or liraglutide).
• Hypersensitivity or contraindication (according to the product circular in the country of the investigational site) to metformin.
• On or likely to require treatment with ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.
• Undergone a surgical procedure within the prior 4 weeks or has major surgery planned during the study.
• History of congenital heart disease or cardiovascular disease other than hypertension.
• Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
• Active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).
• Chronic myopathy, mitochondrial disorder, or a progressive neurological or neuromuscular disorder (e.g., polymyositis, or multiple sclerosis).
• Human immunodeficiency virus (HIV) as assessed by medical history.
• Clinically significant hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndrome).
• Under treatment for hyperthyroidism.
• Exhibits abnormal growth patterns or is being treated with growth hormone.
• History of malignancy or clinically important hematologic disorder.
• History of idiopathic acute pancreatitis or chronic pancreatitis.
• Known history of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year).
• Donated blood products or has had phlebotomy of >10% of estimated total blood volume within 8 weeks of signing informed consent, or intends to donate blood products or receive blood products within the projected duration of the study.
• Pregnant, has a positive urine pregnancy test at Screening Visit/Visit 1, is expecting to conceive within the projected duration of the study, or is breast-feeding.
• Exclusionary laboratory values.
• History of idiopathic acute pancreatitis or chronic pancreatitis.