A Study to Evaluate the Safety, Tolerability, and Efficacy of the Addition of Omarigliptin (MK-3102) to Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy (MK-3102-024)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Omarigliptin; Matching placebo to omarigliptin; Glimepiride; Matching placebo to glimepiride; Insulin glargine; Metformin
Intervention description: Omarigliptin 25 mg capsule administered orally once weekly (preferably on the same day of each week); Matching placebo to omarigliptin capsule administered orally once weekly (preferably on the same day of each week); Glimepiride 1 or 2 mg tablet/capsule administered orally once daily and up-titrated to a maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.; Matching placebo to glimepiride tablet/capsule administered orally once daily and up-titrated to a mock maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.; During Phase B of the study, participants who received a maximum up-titration of open-label glimepiride or blinded glimepiride/matching placebo to glimepiride, may be rescued with open-label insulin glargine.; Participants continue stable pre-study dose of metformin tablet(s) administered orally (>= 1500 mg daily) throughout the study.
Intervention MeSH terms: Metformin; Insulin Glargine; Glimepiride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 402.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the safety and efficacy of omarigliptin compared to
      placebo in participants with inadequate glycemic control on metformin monotherapy. The
      primary hypothesis is that after 24 weeks, the addition of treatment with omarigliptin
      provides greater reduction in hemoglobin A1c (A1C) than placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has type 2 diabetes mellitus

          -  Currently on a stable dose of metformin monotherapy (>=1500 mg per day) for at least
             12 weeks prior to study participation

          -  Male, or female who is not of reproductive potential or if of reproductive potential
             agrees to abstain from heterosexual activity or use (or have their partner use)
             acceptable contraception to prevent pregnancy during the study and for 21 days after
             the last dose of study drug

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus or a history of ketoacidosis

          -  Has been treated with any antihyperglycemic agent (AHA) other than the
             protocol-required metformin within 12 weeks prior to study participation or with
             omarigliptin at any time prior to signing informed consent

          -  History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor

          -  History of intolerance, hypersensitivity, or any other contraindication to metformin,
             glimepiride, or insulin glargine

          -  Is on a weight loss program and is not in the maintenance phase or has been on a
             weight loss medication in the past 6 months or has undergone bariatric surgery within
             12 months prior to study participation

          -  Has undergone a surgical procedure within 4 weeks of study participation or has
             planned major surgery during the study

          -  Is on or likely to require treatment for >=2 consecutive weeks or repeated courses of
             corticosteroids (inhaled, nasal and topical corticosteroids are permitted)

          -  Currently being treated for hyperthyroidism or is on thyroid hormone replacement
             therapy and has not been on a stable dose for at least 6 weeks

          -  Is expecting to undergo hormonal therapy in preparation to donate eggs during the
             period of the trial, including 21 days after the last dose of blinded study medication

          -  History of active liver disease (other than non-alcoholic steatosis) including chronic
             active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease

          -  Human immunodeficiency virus (HIV)

          -  New or worsening signs or symptoms of coronary heart disease or congestive heart
             failure within the past 3 months, or myocardial infarction, unstable angina, coronary
             artery bypass grafting, percutaneous transluminal coronary angioplasty, stroke, or
             transient ischemic attacks in the past 3 months

          -  Poorly controlled hypertension

          -  History of malignancy <=5 years prior to study participation, except for adequately
             treated basal cell or squamous cell skin cancer or in situ cervical cancer

          -  Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic
             syndromes, thrombocytopenia)

          -  Positive urine pregnancy test

          -  Pregnant or breastfeeding, or is expecting to conceive during the study including 21
             days following the last dose of blinded study drug

          -  User of recreational or illicit drugs or has had a recent history of drug abuse

          -  Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or
             engages in binge drinking

          -  Has donated blood products or has had phlebotomy of >300 mL within 8 weeks of study
             participation, or intends to donate blood products within the projected duration of
             the trial or has received, or is anticipated to receive, blood products within 12
             weeks of study participation or within the projected duration of the trial