Glucagon-like Peptide-1 Receptor Agonists and Platelet Function: Potential Benefits Beyond Glycemic Control

There is cumulative evidence that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can offer cardiovascular protection extending beyond glucose-lowering and weight reduction, but the underlying mechanisms contributing to these effects remain incompletely understood. Modulation of platelet function might contribute to the aforementioned benefits. In the current literature review article, we synthesized available preclinical and clinical data evaluating the effects of GLP-1 RAs on platelet activation and function. Preclinical data indicate that GLP-1 RAs might decrease platelet activation via both GLP-1 receptor-dependent and -independent mechanisms with the involvement of cyclic adenosine monophosphate signaling, increase in nitric oxide bioavailability, and suppression of thromboxane-mediated pathways, particularly under inflammatory or shear-stress conditions. Additionally, clinical studies, despite being limited and heterogeneous, support a reduction in platelet activation markers, even independently of glycemic control or weight loss. However, most of them are characterized by small sample sizes and significant heterogeneity among them. In summary, existing evidence suggests that GLP-1 RAs exhibit potential antiplatelet effects that could contribute to their cardioprotective profile. Larger, well-designed clinical studies are crucial to better understand the clinical importance of platelet modulation by GLP-1 RAs and their potential implications for cardiovascular risk reduction.