title: 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.
authors.affiliation: Department of Obstetrics and GynecologyHerlev Gentofte Hospital, Herlev, Denmark machny@dadlnet.dk.|Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.
authors.forename: Malin
authors.initials: M
authors.lastname: Nylander
authors.affiliation: Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.|Department of Internal MedicineEndocrine Unit, Herlev Gentofte Hospital, Herlev, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Frøssing
authors.affiliation: Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.|Department of Internal MedicineEndocrine Unit, Herlev Gentofte Hospital, Herlev, Denmark.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kistorp
authors.affiliation: Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.|Department of Internal MedicineEndocrine Unit, Herlev Gentofte Hospital, Herlev, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
authors.affiliation: Department of Obstetrics and GynecologyHerlev Gentofte Hospital, Herlev, Denmark.|Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.
authors.forename: Sven O
authors.initials: SO
authors.lastname: Skouby
keywords: GLP-1 analog; liraglutide; low-grade inflammation; plasminogen activator inhibitor-1; polycystic ovary syndrome; thrombin generation