Abstract
BackgroundThe efficacy of lifestyle modifications for established obesity is limited in women with polycystic ovary syndrome (PCOS) and more aggressive interventions are needed. We assessed the efficacy and safety of the GLP-1 analogue liraglutide 3mg (LIRA 3mg) versus placebo (PL) for reduction of body weight and hyperandrogenism in women with obesity and PCOSMethodsThis randomized, double-blind, placebo-controlled study enrolled women from a single-outpatient center diagnosed with PCOS (NIH criteria) with a body-mass index of at least 30 kg/m.2 Participants were randomly allocated (2:1) to treatment with a subcutaneous injection LIRA 3mg or visually matching placebo, once daily for 32 weeks, plus lifestyle intervention. Study visits at baseline, and 32 weeks included weight, blood pressure (BP), waist (WC) measures and body composition evaluated by dual-energy X-ray absorptiometry (DXA). Oral glucose tolerance tests (OGTT) were done to assess glycemia, mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), complete metabolic profile and lipid profiles were measured in the fasting sample. Co-primary endpoints were change in body weight (BW) and FAI. Safety was assessed in all patients who received at least one dose of study drug. This study was registered with ClinicalTrials.gov NCT03480022FindingsFrom October 2018 to June 2020, 88 patients were screened, of whom 82 were randomly assigned to LIRA 3mg (n = 55) or PL (n = 27). Change in mean BW from baseline to week 32 was − 5.7% (SE 0·.75) with LIRA 3mg vs. -1.4% (1.09) with PL (P < 0.002). At week 32, more patients on LIRA 3 mg than on placebo achieved weight reductions of at least 5% (25[57%] of 44 vs. 5 [22%] of 23; (p < 0·007). LIRA 3mg resulted in significant reduction of FAI, improvements in SI and IS as well as OGTT MBG, and improved body fat by DXA. Gastrointestinal adverse events, which were mostly mild to moderate, were reported in 32 (58.2%) of 55 patients with LIRA 3mg, and 5 (18.5%) of 27 with PL.InterpretationIn obese women with PCOS, LIRA 3mg once daily achieved a superior and clinically meaningful decrease in BW and androgenicity and improved cardiometabolic parameters compared with placebo.
Metformin AdministrationVersusLaparoscopic Ovarian Diathermy in Clomiphene Citrate-Resistant Women with Polycystic Ovary Syndrome: A Prospective Parallel Randomized Double-Blind Placebo-Controlled Trial
