AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Comparative Venous Outcomes of Glucagon-Like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter-2 Inhibitors in Type 2 Diabetes with Chronic Venous Leg Ulcers
By aggarwal K, Anamika F, Dixit S et al.
Background: Chronic venous leg ulcers (VLUs) are debilitating complications in type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) exert anti-inflammatory and vascular effects beyond glycemic control, yet their comparative impact on venous ulcer outcomes is unknown. Hypothesis: GLP-1RA use is associated with reduced post-thrombotic syndrome (PTS) and venous wound complications versus SGLT2i use in T2DM patients with VLUs. Methods: Using TriNetX (174 healthcare organizations), we performed a retrospective cohort study of adults with T2DM, chronic VLUs, and oral antidiabetic therapy (2017-2025). Patients received GLP-1RAs (semaglutide, liraglutide, or dulaglutide; n=2,776) or SGLT2is (n=3,109) with mutually exclusive exposure. Exclusions: type 1 diabetes, peripheral arterial disease with ulceration, pressure ulcers, metastatic malignancy. Propensity score matching (1:1) balanced demographics, comorbidities, and hemoglobin A1c. The primary outcome was PTS/chronic venous insufficiency at 1, 2, and 5 years. Secondary outcomes (1-year) included amputation/gangrene, cellulitis, debridement, infections (cellulitis, osteomyelitis, sepsis), and a composite wound endpoint. Kaplan-Meier and Cox regression analyses were performed excluding patients with outcomes prior to the index event. Results: After matching (n=1,922/cohort), covariates were balanced (standardized differences<0.05) except body mass index (GLP-1RA 41.9 vs SGLT2i 37.8; standardized difference=0.437). PTS risk did not differ at 1 year (hazard ratio [HR] 0.945, 95% CI 0.774-1.155, p=0.580), 2 years (HR 1.030, 95% CI 0.896-1.185, p=0.675), or 5 years (HR 0.993, 95% CI 0.871-1.131, p=0.910). Five-year event-free survival was similar (30.1% vs 29.7%). One-year secondary outcomes were also comparable: amputation/gangrene (HR 0.876, 95% CI 0.478-1.605, p=0.668), cellulitis (HR 1.167, 95% CI 0.927-1.468, p=0.188), debridement (HR 0.870, 95% CI 0.679-1.115, p=0.269), infections (HR 1.176, 95% CI 0.935-1.480, p=0.164), and composite complications (HR 1.099, 95% CI 0.882-1.370, p=0.400). Conclusion: In this multicenter retrospective study, GLP-1RAs and SGLT2is demonstrated comparable venous wound outcomes in T2DM patients with chronic VLUs across 1- to 5-year follow-up. Clinicians may select between these classes based on cardiometabolic profile without anticipated differential impact on venous wound