AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
GLP-1 Receptor Agonist Add-On Therapy versus Continued SGLT2 Inhibitor Monotherapy and Kidney Failure in Adults with Type 2 Diabetes and CKD Stages 3-4: A Propensity-Matched Real-World Analysis
By Osei - Akuamoah S, Adjei-Sefah K, Kebede Y et al.
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce kidney and cardiovascular risk in chronic kidney disease (CKD), yet residual risk remains substantial. Whether the addition of glucagon-like peptide-1 receptor agonists (GLP-1RA) provides incremental renal and cardiovascular benefit among patients already receiving SGLT2i therapy remains incompletely understood. Methods: Using the TriNetX US Collaborative Network, we identified adults with type 2 diabetes mellitus and CKD stage 3-4 receiving SGLT2 inhibitors who either subsequently initiated GLP-1RA therapy at least 90 days later (combination therapy cohort) or continued SGLT2i monotherapy. Patients with ESRD, kidney transplantation, pregnancy, pancreatitis, or relevant malignancies were excluded. Propensity score matching was performed using 32 variables, including demographics, comorbidities, cardiovascular disease burden, medications, and HbA1c. Outcomes were assessed over 1 year following the index date. Results: Among 131,310 eligible patients, propensity matching yielded 37,267 patients in each cohort. Combination therapy was associated with significantly lower all-cause mortality compared with SGLT2i monotherapy (1.7% vs 3.7%; HR 0.45, 95% CI 0.41-0.50). Kidney failure events were also reduced among patients receiving combination therapy (0.1% vs 0.3%; HR 0.44, 95% CI 0.31-0.62). Furthermore, major adverse cardiovascular events occurred less frequently in the combination therapy group (9.4% vs 12.9%; RR 0.73). Follow-up duration was similar between groups, with a median follow-up of 365 days. Conclusions: Among adults with type 2 diabetes and CKD stages 3-4 already receiving SGLT2 inhibitors, the addition of GLP-1 receptor agonists was associated with lower risks of kidney failure, cardiovascular events, and mortality compared with the continuation of SGLT2 inhibitor monotherapy. These findings support the potential complementary cardiorenal benefits of combined incretin and SGLT2-based therapy in high-risk CKD populations and warrant prospective validation.