Endocrine Abstracts

Glucagon-Like Peptide 1 receptor agonists (GLP1RAs) have been shown to lower the risk of cardiovascular events and death in people with type 2 diabetes at high cardiovascular risk. Danuglipron, is a small molecule peptide agonist of the GLP1 receptor, a novel drug class of oral medication with promising effects on improving glycaemic control and promoting weight loss in people with diabetes or obesity. Due to the early cardiovascular risk reduction observed in some GLP1RA cardiovascular outcomes trials, we hypothesised that part of this risk reduction may be attributed to an effect on platelet aggregation and/or activation. The aim of this study was to measure aggregation and markers of platelet activation in platelets of healthy participants following in-vitro exposure to liraglutide, dulaglutide or danuglipron. Platelet aggregation was measured by light transmission aggregometry using healthy donor platelet rich plasma (PRP). PRP was incubated with vehicle control or liraglutide (20µM), dulaglutide (20µM) or danuglipron (30µM). ADP, arachidonic acid (AA), epinephrine and collagen were used as agonists for aggregation. Resting and AA or ADP-activated platelet surface expression of the activation molecules CD62P and PAC-1 were measured by flow cytometry. One-way repeated measures ANOVA and mixed effects analysis were used to compare control and treatment group means. No significant difference in final aggregation (n = 3-5, P > 0.05), resting and AA-activated expression of CD62P or ADP-activated PAC-1 expression were identified (n = 3/group, P > 0.05) in response to incubation with liraglutide, dulaglutide or danuglipron. In this in-vitro study of healthy donor platelets, treatment with liraglutide, dulaglutide or danuglipron did not alter measures of platelet aggregation or activation.