1186-P: Lean Women with Polycystic Ovary Syndrome and Insulin Resistance Have Normal Incretin Effect, which Is Unaffected by Metformin Therapy

Abstract

Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and a high risk of type 2 diabetes. We investigated the incretin effect (IE) and gastrointestinal-mediated glucose disposal (GIGD) in lean women with PCOS and IR, but normal fasting plasma glucose, and whether metformin affects the IE and GIGD in these women. Ten normoglucose-tolerant, lean women with PCOS and IR (homeostatic model assessment (HOMA-IR) > 1.5) were randomly allocated to receive metformin (500 mg bid) or placebo for 12 weeks interposed by a 6-week wash-out period in a double-blind, cross-over design. The women underwent an OGTT and an isoglycemic intravenous glucose infusion (IIGI) at baseline and at the end of each treatment period. Ten healthy, lean women without PCOS served as controls and underwent one OGTT and one IIGI. At baseline, the control group and the PCOS group had similar age (25±3 vs. 25±4 years (mean±SD), P=0.91), BMI (22±2 vs. 23±2 kg/m2, P=0.42), fasting plasma glucose (4.8±0.3 vs. 5.0±0.2 mmol/l, P=0.11), GIGD (58±15 vs. 59±12%, P=0.84) and IE (56±15 vs. 51±13%, P=0.45); the PCOS group had higher HOMA-IR (1.8±0.4 vs. 1.0±0.3, P<0.0001) and lower Matsuda index (6±3 vs. 9±2, P=0.03). Compared to placebo, 12 weeks’ metformin treatment had no effect on BMI (P=0.42), fasting plasma glucose (P=0.71), HOMA-IR (P=0.95) and Matsuda index (P=0.52). Compared to baseline, metformin treatment lowered the IE in the PCOS group (-9.2% [-17.8;-0.6] (mean [95% CI])), but the change was not different from the change observed after placebo treatment (0.9% [-8.2;10.1], P=0.11) and metformin treatment tended to lower the GIGD (-9.7 [-21.3; 1.9] vs. 1.9% [-10.6; 14.5], P=0.05). We conclude that the studied lean women with PCOS and IR have similar IE and GIGD as matched, insulin-sensitive controls and, surprisingly, we observed no effect of metformin on IR, IE or GIGD in these women. Disclosure L. Vedtofte: None. S. Foghsgaard: None. L. Zierau: None. T. Vilsbøll: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S. Funding Augustinus Foundation; A.P. Møller Foundation