Comparative Renal Effectiveness of GLP-1RA and SGLT2i in US Veterans with Type 2 Diabetes and CKD

Objective: To address limited comparative evidence in older, clinically complex patients with type 2 diabetes and moderate-to-advanced chronic kidney disease (CKD), we compared nephroprotective outcomes after GLP-1RA versus SGLT2i initiation among US Veterans aged ≥65 years with type 2 diabetes and CKD stages 3–4 during 2016–2025. Methods: Within the U.S. Veterans Health Administration database, we identified individuals with type 2 diabetes and CKD stage 3-4 (eGFR 15 to <60 mL/min/1.73 m 2 ) initiating GLP-1RA vs SGLT2i. GLP-1RA formulations approved for weight loss were excluded. The primary outcome was a composite of ESKD, sustained 40% decline in kidney function, or all-cause mortality, with individual components being secondary outcomes. After controlling for >100 covariates including comorbidities, medications, clinical parameters, and laboratory results using propensity score matching weights, we estimated hazard ratios and rate differences. Analyses were stratified by CKD stages, HbA1c, and body mass index. Results: We identified 28,365 GLP-1RA and 78,354 SGLT2i initiators [mean (SD) age: 74 (6) years vs. 76 (6) years]. Over a median follow-up of 11 months, the weighted risks for the primary outcome were similar between treatment groups [HR (95% CI): 1.00 (0.94, 1.07); RD per 1,000 person-years (95% CI): 0.0002 (-0.0037, 0.0042)], mainly attributed to the similar risk for all-cause mortality. The risks of the secondary outcomes were higher in GLP-1RA vs. SGLT2i initiators, but higher risks for sustained kidney function decline and ESKD. Findings were consistent across variations in baseline CKD stage, history of CVD, BMI, and HbA1c level. Absolute rate differences for major kidney disease events and ESKD were larger in patients with more advanced CKD stages. Conclusions: These findings suggest broadly comparable overall kidney and survival outcomes, with potential advantages of SGLT2is for the risks of kidney function decline and incident ESKD across metabolic subgroups in this older adult cohort.