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.

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/m; 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 [SI 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.