Liraglutide in polycystic ovary syndrome: a randomized trial, investigating effects on thrombogenic potential

Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on some markers of VTE and CVD, in PCOS. In a double-blind, placebo-controlled, randomized trial 72 overweight and/or insulin resistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference, from baseline to 26-week follow-up, in change in thrombin generation test parameters: Endogenous thrombin potential, peak thrombin concentration, lag-time and time-to-peak, and in levels of plasminogen activator inhibitor-1. Mean weight loss was 5.2 kg (95%CI 3.0-7.5 kg, p<0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group peak thrombin concentration decreased by 16.71 nmol/L (95%CI 2.32-31.11, p<0.05) and lag-time and time-to-peak increased by 0.13 min (95%CI 0.01-0.25, p<0.05) and 0.38 min (95%CI 0.09-0.68, p<0.05), respectively, but there were no between-group differences. Plasminogen activator inhibitor-1 decreased by 12% (95%CI 0-23, p=0.05) with liraglutide and there was a trend towards 16% (95%CI -4-32, p=0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend towards improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point towards beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.