Abstract 14627: GLP-1 Receptor Agonists, SGLT2 Inhibitors, and Limb and Mortality Outcomes in Patients with Peripheral Artery Disease and Type 2 Diabetes

Abstract

Background: Patients with peripheral artery disease (PAD) and type 2 diabetes mellitus (T2DM) are at high risk of major adverse limb events (MALE), amputation, and mortality. Although GLP1 receptor agonists (GLP1-RAs) and SGLT2 inhibitors improve cardiovascular outcomes, their comparative and combined associations with limb outcomes in PAD remain uncertain. Methods: We conducted a retrospective observational cohort study using the Clalit Health Services electronic medical record database. Patients with PAD and T2DM with cohort entry from 2015 onward were classified into four groups: no GLP1-RA/no SGLT2 inhibitor, GLP1-RA alone, SGLT2 inhibitor alone, and combined GLP1-RA plus SGLT2 inhibitor therapy. Outcomes included MALE, limb revascularization, major and minor amputation, and all-cause mortality. Multinomial propensity scores and stabilized inverse probability of treatment weighting were used to balance baseline covariates, and weighted Cox models estimated hazard ratios. Results: The cohort included 13,471 patients. Median follow-up was 5.75 years for MALE and 4.42 years for mortality. Compared with no therapy, combined GLP1-RA/SGLT2 inhibitor therapy was associated with lower hazards of MALE (HR, 0.50; 95% CI, 0.33-0.75), major amputation (HR, 0.30; 95% CI, 0.17-0.53), and all-cause mortality (HR, 0.23; 95% CI, 0.19-0.28). SGLT2 inhibitor monotherapy was also associated with lower MALE, major amputation, and mortality, while GLP1-RA monotherapy was associated with lower mortality only. Conclusions: Among patients with PAD and T2DM, SGLT2 inhibitor therapy, particularly combined with GLP1-RA therapy, was associated with improved limb and survival outcomes.