Randomized Sitagliptin Withdrawal Study (MK-0431-845)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin; Placebo to sitagliptin; Metformin; Metformin XR; Insulin glargine
Intervention description: Sitagliptin 100 mg, oral, once daily for 30 weeks; Placebo to sitagliptin, 100 mg, oral, once daily for 30 weeks; At least 1500 mg/day, oral, twice daily for participants entering the study on immediate-release metformin + sitagliptin or a fixed dose combination (FDC).; At least 1500 mg/day, oral, once daily for participants entering the study on extended-release metformin + sitagliptin or a FDC.; Insulin glargine (LANTUS®) initiated at 10 units and titrated based on a treat-to-target algorithm to achieve fasting glucose levels of 72-100 mg/dL (4-5.6 mmol/L); administered once daily subcutaneously.
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: 746.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a trial of continuing sitagliptin versus withdrawing sitagliptin in participants with
      Type 2 diabetes mellitus (T2DM) and inadequate glycemic control who initiate and titrate
      insulin glargine (LANTUS®) based on a treat-to-target algorithm to achieve fasting glucose
      levels of 72-100 mg/dL (4-5.6 mmol/L). A primary hypothesis of this trial is that after 30
      weeks, continuing sitagliptin results in a greater reduction of hemoglobin A1C (A1C) relative
      to withdrawing sitagliptin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have T2DM based on American Diabetes Association guidelines

          -  Be on one of the following treatment regimens:

               1. Stable dose of sitagliptin (100 mg/day) and metformin IR or XR (metformin) (≥1500
                  mg/day) either co-administered or as a fixed dose combination (FDC) for ≥12 weeks
                  with A1C between 7.5% and 11.0%, inclusive.

                  OR

               2. Stable dose of metformin (≥1500 mg/day) and another dipeptidyl peptidase-4
                  (DPP-4) inhibitor (at maximum labeled dose, other than sitagliptin, either
                  co-administered or as a FDC, for ≥12 weeks with A1C between 7.5% and 11.0%,
                  inclusive.

                  OR

               3. Stable dose of sitagliptin (100 mg/day) and metformin (≥1500 mg/day) either co
                  administered or as a FDC, and a sulfonylurea for ≥12 weeks OR stable dose of
                  metformin (≥1500 mg/day) and a sulfonylurea administered as a FDC and sitagliptin
                  (100 mg/day) with A1C between 7.0% and 10.0%, inclusive.

                  OR

               4. Stable dose of metformin (≥1500 mg/day) and another DPP-4 inhibitor (at maximum
                  labeled dose), other than sitagliptin, either co-administered or as a FDC, and a
                  sulfonylurea for ≥12 weeks OR stable dose of metformin (≥1500 mg/day) and a
                  sulfonylurea administered as a FDC and another DPP-4 inhibitor other than
                  sitagliptin with A1C between 7.0% and 10.0%, inclusive OR

               5. Stable dose of metformin (≥1500 mg/day) and a sulfonylurea either co-administered
                  or as a FDC for ≥12 weeks with A1C between 7.5% and 11.0%, inclusive.

          -  Meet one of the following categories:

               1. The participant is a male

               2. The participant is a female who is not of reproductive potential

               3. The participant is a female who is of reproductive potential and agrees to avoid
                  becoming pregnant while receiving study drug and for 14 days after the last dose
                  of study drug by practicing abstinence from heterosexual activity OR use (or have
                  her partner use) acceptable contraception during heterosexual activity

        Exclusion Criteria:

          -  Has been treated with any anti-hyperglycemic agent (AHA) other than protocol-specified
             agents (i.e., other than metformin, DPP-4 inhibitor, or sulfonylurea agent) within the
             prior 12 weeks.

          -  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 type 1 diabetes mellitus (T1DM) or ketoacidosis, or has a history of
             latent autoimmune diabetes of adults (LADA), is assessed by the investigator as
             possibly having T1DM or LADA confirmed with a C-peptide <0.7 ng/mL (<0.23 nmol/L), or
             has a history of other specific types of diabetes (e.g., genetic syndromes, secondary
             pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, or
             post-organ transplant).

          -  Is assessed by the investigator to be not appropriate for, or does not agree to
             target, a fasting glucose of 72-100 mg/dL (4.0-5.6 mmol/L).