AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Comparative Cardiovascular Outcomes of SGLT2 Inhibitors versus DPP-4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matched Real-World Analysis
By Ahmed Khan S, Marasini A
Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are commonly used second-line agents in type 2 diabetes mellitus (T2DM). This large-scale real-world analysis compared their effects on major cardiovascular, renal, and diabetes-related complications. Methods: Using the TriNetX Research network (109 healthcare organizations), we identified 728,124 patients initiating SGLT2i and 473,812 initiating DPP4i, all with T2DM and aged ≥18 years, excluding those with type 1 diabetes. Propensity score matching (1:1) balanced cohorts to 300,614 patients each. Index date was the first prescription of the respective drug class. Outcomes were assessed from 1 day to 1,825 days (5 years) post-index. Risks, risk ratios, hazard ratios (HR), and survival probabilities were evaluated using risk analysis, Kaplan-Meier, and number-of-instances methods, with exclusion of patients having the outcome prior to the time window. Results: After matching, SGLT2i use was associated with lower risk of several key outcomes compared to DPP4i. All-cause mortality was markedly reduced (7.1% vs 12.4%; risk ratio 0.570, 95% CI 0.561-0.579; HR 0.519, 95% CI 0.510-0.528; log-rank p<0.001), with 5-year survival of 88.90% vs 79.50%.Cardiovascular benefits included lower cerebral infarction (3.2% vs 3.7%; risk ratio 0.858, 95% CI 0.834-0.882; HR 0.783, 95% CI 0.761-0.806), heart failure (7.4% vs 7.6%; risk ratio 0.969, 95% CI 0.951-0.989; HR 0.857, 95% CI 0.839-0.874), and cardiac arrest (1.0% vs 1.4%; risk ratio 0.671, 95% CI 0.640-0.703; HR 0.616, 95% CI 0.587-0.646). Myocardial infarction risk was similar (3.6% vs 3.5%; risk ratio 1.022, p=0.114), though survival analysis favored SGLT2i (HR 0.928).Renal outcomes showed lower acute kidney injury (AKI) with SGLT2i (8.4% vs 9.9%; risk ratio 0.853, 95% CI 0.839-0.868; HR 0.768) and a modest reduction in chronic kidney disease (CKD) progression (11.8% vs 12.1%; risk ratio 0.976; HR 0.872). Diabetic polyneuropathy (6.3% vs 5.3%; risk ratio 1.178) and ophthalmic complications (5.4% vs 4.5%; risk ratio 1.205) were higher with SGLT2i, while diabetic foot events were marginally increased (2.1% vs 2.0%; risk ratio 1.048). Number of event instances was generally lower or comparable with SGLT2i across most outcomes. Conclusions: In this large propensity score-matched real-world cohort of patients with T2DM, SGLT2i initiation was associated with substantially lower all-cause mortality, reduced cardiovascular events (particularly stroke, heart failure, and cardiac arrest), and better renal outcomes compared to DPP4i over 5 years, supporting the preferential use of SGLT2i in appropriate patients.