Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM

• Status: Completed
• Trial end date: 2017-09-28
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Woman's
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate

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)