Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM
Condition: Disorder of Glucose Regulation
Intervention: Sitagliptin-Metformin; Metformin; Placebo pill
Intervention description: Experimental -dipeptidyl peptidase-4 (DPP-4) inhibitor- oral medication; Biguanide- insulin sensitizer; Will evaluate effect of lifestyle and diet only
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 36.0
Sex: Female
Minimum age: 18 Years
Maximum age: 42 Years
Healthy volunteers: No
Keywords: prediabetes; impaired fasting/impaired glucose tolerance; post gestational diabetes; diabetes prevention

Summary:

      Gestational diabetes mellitus (GDM) is defined as "any degree of glucose intolerance with
      onset or first recognition during pregnancy." GDM is one of the most frequent metabolic
      disorders occurring during pregnancy. Approximately 7% of all pregnancies in the United
      States are complicated by gestational diabetes resulting in more than 200,000 cases annually.
      There is epidemiologic evidence associating GDM with insulin resistance, glucose intolerance,
      and type 2 diabetes (DM2). Among all the risk factors of diabetes mellitus, the experience of
      gestational diabetes is the strongest one. Systematic reviews of older studies conclude that
      35-60% women with gestational diabetes will develop type 2 diabetes at rates much greater
      than control groups who did not have glucose intolerance during pregnancy. Studies are needed
      for optimal postpartum and long-term health of women who have had GDM. Recent evidence
      suggests that incretin-based therapies may be useful for the treatment of DM2 because
      continuous administration of glucagon-like peptide 1 (GLP-1) produces substantial
      improvements in glucose control and ß-cell function in subjects with DM2. Inhibition of
      dipeptidyl peptidase-4 (DPP-4) increases the concentration of GLP-1 and may potentially delay
      disease progression in GDM considering the ß-cell function improvement in DM2 and ß-cell mass
      shown to increase in animal models. This study will examine if combination sitagliptin (a
      DPP-4 inhibitor)-plus metformin is more effective than metformin alone or placebo in
      improving metabolic parameters, specifically the impact on β-cell function, in prior GDM
      women with glucose abnormalities.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females 18 years to 42 years of age who experienced gestational diabetes mellitus
             (GDM) during recent (within 12 months) pregnancy with prediabetic hyperglycemia
             determined by an oral glucose tolerance test (OGTT) with 75 g glucose postpartum.
             Study subjects will be inclusive of prior GDM women with impaired fasting glucose
             (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT) postpartum.

          -  Written consent for participation in the study

        Exclusion Criteria:

          -  Cholestasis during the past pregnancy

          -  Any hepatic diseases in the past (viral hepatitis, toxic hepatic damage, jaundice of
             unknown etiology)

          -  Serum aspartate transaminase (AST) and/or alanine aminotransferase (ALT) level
             exceeding more than twice normal lab values

          -  Presence of hypersensitivity to sitagliptin or other DPP-4 inhibitor

          -  Current use of metformin, thiazolidinediones, GLP-1 receptor agonists, DPP-4
             inhibitors, or weight loss medications (prescription or over the counter [OTC])

          -  Prior use of medication to treat diabetes except gestational diabetes

          -  Use of drugs known to exacerbate glucose tolerance

          -  History of diabetes or prior use of medications to treat diabetes except GDM

          -  Creatinine clearance less than 60 ml/min

          -  Pregnancy planned during the coming two years

          -  Currently lactating

          -  Patient not willing to use adequate contraception during study period (unless
             sterilized)