A Study to Assess the Addition of Sitagliptin to Metformin Compared With the Addition of Dapagliflozin to Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) and Mild Renal Impairment Who Have Inadequate Glycemic Control on Metformin With or Without a Sulfonylurea (MK-0431-838)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin; Dapagliflozin; Metformin; Matching placebo to sitagliptin; Matching placebo to dapagliflozin; Sulfonylurea
Intervention description: Sitagliptin 100 mg oral tablet; Dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Dapagliflozin 10 mg daily may be down-titrated to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator.; This medication is a standard-of-care medication and is administered in an open-label fashion. Supply of background metformin oral tablet(s) (at least 1500 mg daily) will be the responsibility of the participant throughout the duration of the study.; Matching placebo to sitagliptin 100 mg oral tablet; Matching placebo to dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to matching placebo to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Matching placebo to dapagliflozin 10 mg daily may be down-titrated to matching placebo to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator.; This medication is a standard-of-care medication and is administered in an open-label fashion. The dose of the sulfonylurea agent will be required to be at least 50% of maximum labeled dose, consistent with near maximum efficacy of the sulfonylurea agent.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 614.0
Sex: All
Minimum age: 25 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to assess the effect of the addition of sitagliptin to metformin
      with or without a sulfonylurea compared with the addition of dapagliflozin to metformin with
      or without a sulfonylurea on hemoglobin A1c (A1C) over 24 weeks of treatment as well as the
      overall safety and tolerability of sitagliptin in comparison to that of dapagliflozin after
      24 weeks of treatment. The primary hypothesis is that the change from baseline in A1C in
      participants treated with the addition of sitagliptin is non-inferior compared to that in
      participants treated with the addition of dapagliflozin after 24 weeks of treatment.
    

Eligibility criteria:

        Inclusion Criteria

          -  Have T2DM at Screening visit

          -  Be on metformin monotherapy ≥1500 mg/day alone or in combination with an sulfonylurea
             agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational
             site) for ≥8 weeks

          -  Is a male or a female not of reproductive potential (defined as one who is
             postmenopausal or has had a hysterectomy and/or bilateral oophorectomy, or had
             bilateral tubal ligation or occlusion at least 6 weeks prior to Screening visit). If
             participant is a female of reproductive potential, must agree to remain abstinent from
             heterosexual activity or agrees to use (or have her partner use) acceptable
             contraception to prevent pregnancy while receiving blinded study drug and for 14 days
             after the last dose of blinded study drug

        Exclusion Criteria:

          -  Has a history of type 1 diabetes mellitus or a history of ketoacidosis

          -  Has a history of secondary causes of diabetes

          -  Has a known hypersensitivity or intolerance to any dipeptidyl peptidase IV (DPP-4)
             inhibitor or sodium-glucose cotransporter 2 (SGLT2) inhibitor

          -  Has been treated with any anti-hyperglycemic agents (AHA) other than metformin and for
             participants on dual combination therapy, a sulfonylurea within 12 weeks of screening

          -  Intends to initiate weight loss medication during the study period

          -  Has undergone bariatric surgery within 12 months of Screening visit

          -  Has started a weight loss medication or a medication associated with weight changes
             within the prior 12 weeks.

          -  Has a history of myocardial infarction, unstable angina, arterial revascularization,
             stroke, transient ischemic attack, heart failure within 3 months of Screening visit

          -  Has a history of malignancy ≤5 years prior to study, except for adequately treated
             basal cell or squamous cell skin cancer or in situ cervical cancer

          -  Has human immunodeficiency virus (HIV)

          -  Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells,
             or clinically important hematological disorder (such as aplastic anemia,
             myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

          -  Has a medical history of active liver disease (other than non-alcoholic hepatic
             steatosis), including chronic hepatitis B or C, primary biliary cirrhosis, or
             symptomatic gallbladder disease

          -  Is currently being treated for hyperthyroidism or is on thyroid replacement therapy
             and has not been on a stable dose for at least 6 weeks prior to Screening visit

          -  Is on or likely to require treatment for ≥14 consecutive days or repeated courses of
             corticosteroids

          -  Is on or likely to require treatment for ≥7 consecutive days with non-steroidal
             anti-inflammatory drugs

          -  Is pregnant or breast-feeding, or is planning to conceive during the study, including
             14 days following the last dose of blinded study drug

          -  Is planning to undergo hormonal therapy in preparation to donate eggs during the
             study, including 14 days following the last dose of blinded study drug

          -  Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or
             engages in binge drinking

          -  Has donated blood or blood products within 6 weeks of Screening visit or who plans to
             donate blood or blood products at any time during the study