ESC Congress 2026 Abstract · Oct 26, 2026

Cardiovascular–kidney–metabolic risk stratification and cardiorenal outcomes with SGLT2 inhibitors versus GLP-1 receptor agonists in type 2 diabetes: a global federated network study

By Wang C, Askarinejad A, Chen Y et al.

Background: Obesity is common among patients with type 2 diabetes (T2D) and cardiovascular–kidney–metabolic (CKM) comorbidities, yet the comparative effectiveness of SGLT2 inhibitors (SGLT2i) versus GLP-1 receptor agonists (GLP-1RA) remains uncertain. Purpose: We compared obese versus non-obese risk profiles and evaluated SGLT2i versus GLP-1RA for major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE), stratified by obesity status and CKM comorbidity burden. Methods: We conducted a retrospective cohort study using TriNetX including adults with T2D between 2013 and 2024. Patients were classified by CKM comorbidity burden: low CKM risk (CKM0–1, one or none of hypertension, chronic kidney disease, or hyperlipemia); moderate CKM risk (CKM2, two comorbidities); high CKM risk (CKM3, all three comorbidities, metabolically extremely unhealthy). Within each CKM risk group, patients were further stratified by obesity status (BMI ≥30 kg/m²). Primary outcomes were MACE and MAKE. Secondary outcomes included heart failure (HF), atrial fibrillation (AF), and all-cause mortality. Propensity score matching (PSM) and Cox regression were applied. Results: After PSM, obese patients in the high CKM risk group had higher risks of HF (HR 1.35, 95% CI 1.33–1.37), AF (HR 1.33, 95% CI 1.31–1.35), MACE (HR 1.03, 95% CI 1.01–1.04), and MAKE (HR 1.06, 95% CI 1.04–1.08) compared with non-obese patients [Figure1]. Within the high CKM risk group, SGLT2i were associated with lower MAKE compared with GLP-1RA in both obese (HR 0.55, 95% CI 0.50–0.61) and non-obese patients (HR 0.48, 95% CI 0.41–0.56). In contrast, SGLT2i were associated with higher risks of MACE compared with GLP-1RA in obese (HR 1.34, 95% CI 1.25–1.44) and non-obese patients (HR 1.18, 95% CI 1.07–1.30). A consistent cardiorenal benefit pattern was observed across low, moderate and high CKM strata, with SGLT2i reducing renal outcomes and GLP-1RA conferring greater cardiovascular protection. Compared with SGLT2i, GLP-1RA were associated with lower all-cause mortality among obese patients with low and moderate CKM risk (low CKM risk: HR 1.27, 95% CI 1.19–1.36; moderate CKM risk: HR 1.13, 95% CI 1.06–1.21) [Figure2]. Conclusion: Obesity in patients with high CKM risk was associated with increased risks of MACE, MAKE, HF, and AF. SGLT2i were associated with lower risks of MAKE, whereas GLP-1RA were associated with lower risks of MACE, HF, and AF. Among obese patients with low or moderate CKM risk, GLP-1RA were associated with lower all-cause mortality.Obese vs non-obese cardiorenal outcomesSGLT2i vs GLP-1RA across obesity strata

doi.org/10.1093/eurheartj/ehag785.3493Open accessInterventions