Study of Sitagliptin for the Treatment of Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Insulin (MK-0431-260)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin; Comparator: Placebo; Insulin Glargine; Metformin
Intervention description: Sitagliptin 100 mg tablet once daily for 24 weeks; Placebo to sitagliptin once daily for 24 weeks; Participants on insulin glargine or another insulin regimen for at least 10 weeks prior to screening will continue or switch to open-label insulin glargine once-daily in the evening for the duration of the study.; Participants on metformin oral tablet(s) at a dose of at least 1500 mg/day for at least 10 weeks prior to screening will continue receiving metformin at their current dose for the duration of the study.
Intervention MeSH terms: Metformin; Insulin Glargine; Sitagliptin Phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 660.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to examine the insulin-sparing effect of sitagliptin 100 mg
      once-daily compared with placebo over 24 weeks in participants with type 2 diabetes mellitus
      who have inadequate glycemic control on insulin alone or in combination with metformin. The
      primary hypothesis of this study is that after 24 weeks, sitagliptin reduces the dose of
      insulin relative to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  has type 2 diabetes mellitus

          -  has one of the following criteria:

               -  diagnosed with diabetes after age 40 years and insulin therapy was initiated at
                  least 3 years following diagnosis

               -  if diagnosed with diabetes under age 40 years or insulin started earlier than 3
                  years after diagnosis, has a fasting C-peptide greater than 0.7 ng/mL

          -  must be at least 18 years of age and less than or equal to 80 years of age (for
             participants in India: must be at least 18 years of age and less than or equal to 65
             years of age)

          -  on a stable regimen of insulin for at least 10 weeks with or without metformin (at
             least 1500 mg/day) and/or sulfonylurea for at least 10 weeks

          -  is highly unlikely to become pregnant (not of reproductive potential or agrees to
             remain abstinent or use (or have their partner use) an acceptable method of birth
             control during the study and for 14 days after the last dose of study medication

        Exclusion Criteria:

          -  has been treated with a dipeptidyl peptidase IV (DPP-4) inhibitor, a thiazolidinedione
             (TZD), or a glucagon-like peptide-1 (GLP-1) mimetic or analogue, within the past 12
             weeks

          -  currently on treatment with daily use (one or more injections per day) of a

        pre-prandial short-acting or rapid-acting insulin alone or as part of a basal/bolus insulin
        regimen

          -  has symptomatic hyperglycemia that requires immediate initiation, adjustment, or
             addition of antihyperglycemic therapy

          -  has a history of 2 or more episodes of hypoglycemia resulting in seizure,

        coma, or loss of consciousness, - or - has had recurrent (≥3 times per week) episodes of
        hypoglycemia over the past 8 weeks

          -  has a history of ketoacidosis

          -  is not appropriate for or does not agree to target a fasting glucose of 72-100 mg/dL
             [4.0-5.6 mmol/L]

          -  is on or likely to require treatment with corticosteroids

          -  has undergone a surgical procedure within 4 weeks or has planned major surgery during
             the study

          -  is currently being treated for hyperthyroidism or is on thyroid hormone

        therapy and has not been on a stable dose for at least 6 weeks

          -  has a history of active liver disease (other than non-alcoholic hepatic

        steatosis)

          -  has had new or worsening signs or symptoms of coronary heart disease or

        congestive heart failure within the past 3 months, or has any of the following

        disorders within the past 3 months:

          -  acute coronary syndrome

          -  coronary artery intervention

          -  stroke or transient ischemic neurological disorder

               -  has a systolic blood pressure greater than 160 mm Hg or a diastolic blood
                  pressure greater than 90 mm Hg

               -  has human immunodeficiency virus (HIV)

               -  has severe peripheral vascular disease

               -  has a clinically important hematological disorder

               -  has a history of malignancy that is less than 5 years from study start, except
                  for adequately treated basal cell or squamous cell skin cancer or in situ
                  cervical cancer

               -  has a positive urine pregnancy test

               -  is pregnant or breast-feeding, or is expecting to conceive or donate eggs

        during the study

          -  a user of recreational or illicit drugs or has had a recent history of drug abuse