Metformin and Sitagliptin in Women With Previous Gestational Diabetes

A randomized, double blinded study, on 45 women with previous gestational diabetes and impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) to assess the effects of a 4-month treatment with metformin and/or a dipeptidyl peptidase-4 inhibitor (sitagliptin) on beta-cell function and insulin resistance.

At baseline, all women will have a standardized medical history, physical, and laboratory examination. Plasma glucose, insulin, pro-insulin, C-peptide, glucagon, adipokines, pro-inflammatory molecules, and lipid profile will be determined in fasting condition. A 75g OGTT will be performed after an overnight fasting and sample will be drawn at 15, 30, 60, 90 and 120 minutes for plasma glucose, C-peptide, glucagon and GLP-1 determinations. Women with IFG or IGT will be recruited and undergo to a hyperglycemic clamp with arginin bolus at the end of the test. Then the women will be randomized in 3 treatment groups: metformin (850 mg bid), sitagliptin (100 mg qd)or metformin (850 mg bid) + sitagliptin (100 mg qd). After 4-month treatment, the baseline evaluation will be repeated.

Inclusion criteria

• Female subjects aged ≥18 and ≤45 years
• Caucasian race
• History of previous gestational diabetes (in the screening) during pregnancy.
• Female of childbearing potential must use effective contraceptive measures for at last 1 month prior to entry into the study and should continue to use the some contraceptive method during the overall study period
• Written informed consent obtained

Exclusion criteria

• Patients diagnosed with type 1 insulin dependent diabetes
• Diagnosis of diabetes in the 75g OGTT performed at entry
• BMI ≤18 or ≥50 Kg/m2
• Chronic impaired renal function
• Impaired liver function as shown by transaminase levels ≥ twice above the upper normal range
• History of hypersensitivity to metformin
• Pregnant or breast-feeding women, or women planning to become pregnant during the study
• Failure to use adequate contraception (Women of current reproductive only)
• Mental condition rending the subject unable to understand the nature, scope and possible consequences of the study
• Any clinically significant major organ system disease
• Patients with underlying concomitant medication requiring a long-term use of drugs potentially acting on glucose metabolism (e.g. corticosteroids, diuretics, beta-adrenergic drugs or others)
• Treatment or likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
• History of drug or alcohol abuse within the last 2 years or current addiction to substances of abuse
• Any disease or condition that in the opinion of the investigator may interfere with the completion of the study
• Subjects unlikely to comply with the protocol