Postpartum treatment with liraglutide in combination with metformin versus metformin monotherapy to improve metabolic status and reduce body weight in overweight/obese women with recent gestational diabetes: A double-blind, randomized, placebo-controlled study

Abstract Background Gestational diabetes (GDM) imparts a high risk of developing diabetes postpartum. Insulin resistance appears to be the major contributor. Liraglutide, a glucagon-like peptide-1 analogue, improves peripheral glucose disposal and reduces body weight. We evaluated whether liraglutide in combination with metformin (MET-LIRA) is more effective than metformin monotherapy (MET-P) in improving insulin action and reducing body weight in overweight prior GDM (pGDM) women. Methods Women (n = 153; body mass index (BMI) ≥25 kg/m2; 18–45 y; GDM within 12 months) with metabolic abnormalities were randomized to MET-LIRA (MET-2000 mg, LIRA 1.8 mg SC QD) or MET-P (MET-2000 mg, Placebo QD). Study visits at baseline, 36–40, 56–60 and 80–84 weeks included body weight (BW), BMI, waist circumference and waist-to-height ratio measures. Oral glucose tolerance tests (OGTTs) were performed to assess glycemia, mean blood glucose (MBG), lipids, and compute insulin sensitivity and secretion measures. Findings Seventy-two (47%) participants completed the study. MET-LIRA therapy was significantly better in improving MBG and insulin sensitivity indices [SIOGTT MET-LIRA from 4.6 (3.2) to 5.9 (2.9) vs. MET-P 5.5 (3.0) to 5.4 (3.2)] and reducing BW and central adiposity [BMI MET-LIRA from 37.2 (8.3) to 33.8 (5.2) vs MET-P 33.8(5.2) to 32.8(6)]. MET–LIRA therapy but not MET-P decreased triglycerides (TRG) and TRG/high density lipoprotein cholesterol (HDL-C) ratios. Interpretation MET-LIRA treatment demonstrated superior efficacy in correcting the metabolic status of pGDM women over 84 weeks of therapy. The addition of liraglutide to metformin therapy resulted in a more dramatic decrease in BW and central adiposity than metformin alone. Fundation Supported by an unrestricted investigator initiated grant from Novo Nordisk, Inc. awarded to K.E.H. Meeting presentation The results from preliminary analyses of this study were presented at 76th meeting of the American Diabetes Association, June 10–14, 2016 New Orleans, LA, and 77th meeting of the American Diabetes Association, June 9–12, 2017San Diego, CA.