Association of GLP-1 Receptor Agonist Exposure with Platelet Function in Patients with Diabetes and Peripheral Artery Disease After Lower-Extremity Revascularization

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiovascular outcomes in patients with type 2 diabetes and have emerging relevance in peripheral artery disease (PAD), but their association with platelet function after lower-extremity revascularization is uncertain. We evaluated whether active GLP-1RA exposure was associated with thromboelastography with platelet mapping (TEG-PM) and global hemostatic parameters in patients with diabetes and PAD. Methods: We retrospectively analyzed prospectively collected serial TEG data from adults with diabetes and PAD undergoing lower-extremity revascularization between December 2022 and December 2025. GLP-1RA exposure was defined as active use at each blood draw and treated as time-varying. Platelet outcomes were analyzed using linear mixed-effects models adjusted for nonlinear elapsed time, insulin, aspirin, clopidogrel, ticagrelor, age, sex, body mass index, renal function, coronary artery disease, and hypertension. False discovery rate (FDR) correction was applied within prespecified ADP and arachidonic acid (AA) outcome families. Results: The cohort included 178 patients contributing 462 scheduled measurements; 20 patients contributed 47 GLP-1RA-exposed measurements. At baseline, 13 of 169 patients were receiving a GLP-1RA. Adjusted GLP-1RA-associated differences were −1.98 percentage points for ADP aggregation (95% CI, −10.9 to 6.89; FDR-adjusted p = 0.815), −0.64 mm for ADP maximum amplitude (MA) (95% CI, −6.06 to 4.77; FDR-adjusted p = 0.815), −0.45 percentage points for AA aggregation (95% CI, −13.5 to 12.6; FDR-adjusted p = 0.947), and −1.63 mm for AA-MA (95% CI, −8.28 to 5.03; FDR-adjusted p = 0.947). Global TEG outcomes and GLP-1RA-by-insulin interactions were not significant. The strongest time interaction was observed for ADP-MA (omnibus p = 0.072; FDR-adjusted p = 0.145). Conclusions: No statistically significant associations were detected between active GLP-1RA exposure and pathway-specific platelet reactivity or global hemostatic parameters in this longitudinal PAD cohort. Estimates remained imprecise, and effects of potentially clinically relevant magnitude could not be excluded. The descriptive ADP-mediated temporal pattern warrants prospective evaluation in larger cohorts.