Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM
Condition: Disorder of Glucose Regulation
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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.

      Gestational diabetes is often the culmination of years of unrecognized and unmodified
      diabetes risk factors that lead to overt and occult clinical manifestations during pregnancy.
      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. The higher rates were in studies of particular ethnic groups in
      the U.S. Presently, in the literature, there are described new, more efficient methods of
      diabetes prevention in groups with a high risk of this disorder, which involve both,
      lifestyle modification and pharmacological therapies. Lifestyle intervention was found to
      reduce the incidence of type 2 diabetes by 58% and metformin by 31% as compared with placebo.
      Studies are needed for optimal postpartum and long-term health of women who have had GDM.
      Considerable 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
      type 2 diabetes. 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-plus metformin is more effective than metformin alone or
      placebo in improving metabolic parameters, specifically the impact on β-cell function, in
      at-risk women with a recent history of GDM.
    

Intervention name(s): Sitagliptin-Metformin; Metformin; Placebo pill
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Experimental -dipeptidyl peptidase-4 (DPP-4) inhibitor- oral medication; Biguanide- insulin sensitizer; Will evaluate effect of lifestyle and diet only
Other intervention name(s): Janumet; Glucophage; placebo control
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: prediabetes; impaired fasting/impaired glucose tolerance; post gestational diabetes; diabetes prevention