Effects of the antidiabetic drug metformin of platelet activation and ex vivo thrombus formation

Introduction Abdominal aortic aneurysm (AAA) is characterised by the progressive fragmentation of the extracellular matrix (ECM) and chronic inflammation in the aortic tissue, resulting in an irreversible dilatation of the abdominal aorta. Beside this, vascular smooth muscle cell apoptosis, and the formation of a platelet-rich intraluminal thrombus are additional pathophysiological hallmarks of AAA development [ 1 ] [ 2 ]. It was recently shown that platelet hyperreactivity directly contributes to AAA formation by promoting ECM remodelling, as well as immune cell infiltration, resulting in a compromised aortic wall integrity [ 3 ] [ 4 ]. Despite extensive efforts to develop pharmacological approaches in order to target AAA growth, to date no drug-based therapy has demonstrated clinical efficacy. Thus, elucidating the molecular mechanisms, driving AAA initiation and progression is crucial to identify novel therapeutic targets. In his context different studies reported beneficial effects of the antidiabetic drug metformin AAA incidence and growth [ 5 ]. Therefore, we here investigated the effects on metformin on basal platelet function, to assess whether metformin treatment has the potential to attenuate platelet hyperreactivity in the context of AAA. Method Flow cytometric analysis of platelet degranulation, integrin α IIb β 3 activation, platelet-leukocyte aggregate formation, and pro-coagulant activity upon metformin treatment. Effects of metformin on ex vivo thrombus formation. Results In order to investigate the effects of metformin on the basal platelet function, human whole blood samples from healthy volunteers were pretreated with 20 mM of metformin for 1h. The flow cytometric analysis revealed a significantly attenuated Integrin α IIb β 3 activation (PAC-1) of platelets upon metformin treatment. Thereby, integrin α IIb β 3 activation was reduced under resting conditions, as well as upon stimulation with various agonists, including ADP, PAR4, and CRP. In contrast, platelet degranulation assessed via P-selection externalization, was predominantly unaltered. However, the pro-coagulant activity of metformin treated platelets was shown to be significantly reduced under resting conditions and upon activation with low dose of CRP, indicated by decreased AnnexinV-binding to platelet. In addition, the formation of circulating platelet-leukocyte aggregates was substantially reduced after metformin treatment. Functionally, these effects of metformin on platelet function culminated in a significantly attenuated ex vivo thrombus formation under arterial shear rates using the Maastricht flow chamber system. Conclusion In conclusion, treatment with metformin directly effects platelet activation, as well as ex vivo thrombus formation. Thus, metformin may represent a promising candidate in order to target platelet hyperreactivity reported in patients with AAA and therefore reduce platelet-mediated effects in AAA formation. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany