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

Abstract

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 markers of VTE and CVD risk, 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 in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. 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. There was a trend toward 12% (95% CI 0–23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI −4 to 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 toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.

Pharmacologic therapy to induce weight loss in women who have obesity/overweight with polycystic ovary syndrome: a systematic review and network meta‐analysis

“…Participants aged 18 years to menopause were included in 24 studies, and two studies examined the effect of metformin on weight reduction in adolescent women . Apart from two studies where liraglutide 1.8 mg d −1 for 26 weeks and 3.0 mg d −1 for 12 weeks were applied , 1.2 mg d −1 was used for 12 weeks in the remaining five studies examining the efficacy of liraglutide. The use of liraglutide1.2 mg d −1 in combination with metformin 2.0 g d −1 was identified in four trials .…”

“…because of insufficient information. Low risk, some concerns and high risk of allover bias were found in 9 (34.6%) , 10 (38.5%) and 6 (23.1%) RCTs. The high risk of allover bias originated from missing outcome data and selection of the reported results .…”

Effect of liraglutide on ectopic fat in polycystic ovary syndrome: A randomized clinical trial

“…The LIPT‐study was a double‐blind, placebo‐controlled RCT . In short, inclusion criteria were PCOS (Rotterdam criteria), BMI > 25 kg/m 2 and/or presence of IR.…”

“…Therefore, we performed a randomized clinical trial (RCT) investigating whether monotherapy with the GLP‐1RA liraglutide could reduce liver fat content, VAT and the prevalence of NAFLD in women with PCOS. The present study is a secondary analysis of data from the LIPT‐study (Liraglutide in PCOS on Markers of Vascular Thrombosis) …”

“…The present study is a secondary analysis of data from the LIPT-study (Liraglutide in PCOS on Markers of Vascular Thrombosis). 8…”