Abstract 818: Plasminogen Activator Inhibitor-1 is Reduced by the Once-Daily Human Glucagon-Like Peptide-1 Analog Liraglutide When Used in the Treatment of Type 2 Diabetes
The abnormalities in lipid/CV biomarker profiles in patients with T2D are associated with increased CV risk. The human GLP-1 analog, liraglutide, improves A1C by 1.0 –1.5%, produces sustained weight reductions of 2–3 kg and reduces SBP by 2– 6 mmHg independent of weight loss in these patients. Liraglutide has also been shown to improve lipid profiles (total cholesterol, LDL, VLDL, HDL) and CV biomarkers such as brain natiuretic peptide (BNP; decreased 12%) and high sensitivity C-reactive protein (hsCRP; decreased 23%). Increased levels of plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of the fibrinolytic system produced by endothelial cells and adipocytes, has been raised as a potential biomarker and candidate mediator for CV risk, perhaps especially in diabetes. In vitro in human endothelial cells, liraglutide reverses hyperglycemia-induced PAI-1 elevation. Data from six Phase 3 clinical trials (LEAD 1– 6; n=3967) comparing liraglutide 1.8 mg with standard therapy (glimepiride, rosiglitazone, exenatide, insulin glargine and placebo) in patients with T2D were used in a meta-analysis (ANCOVA) to assess the effect of liraglutide on circulating PAI-1 levels. PAI-1 was measured by coagulometry in citrated plasma from blood samples collected at baseline and week 26. The change in PAI-1 from baseline was significant (p=0.0008) for 1.8 mg liraglutide with estimated relative change of −7.6% but not for any other treatment groups, where estimated relative change varied from −1.4% to 1.1%. These meta-analysis data suggest liraglutide 1.8 mg daily may decrease plasma PAI-1 levels in patients with T2D, with potential implications for CV risk in the setting of diabetes.