SGLT2 Inhibitors vs GLP-1 Receptor Agonists for Kidney Outcomes in Individuals With Type 2 Diabetes

Importance No randomized clinical trial has directly compared the effectiveness of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment in reducing acute and chronic kidney outcomes. Objective To examine the comparative effectiveness of SGLT2i and GLP-1RA treatment for acute and chronic kidney outcomes in individuals with type 2 diabetes. Design, Setting, and Participants This comparative effectiveness study with a target trial emulation design used nationwide, population-based data from Denmark. Participants were individuals with metformin-treated type 2 diabetes who initiated SGLT2i or GLP-1RA treatment from January 2014 to November 2020, with follow-up through October 2024. Exposure Initiation of an SGLT2i or a GLP-1RA. Main Outcomes and Measures The 2 coprimary outcomes were chronic kidney disease (CKD; 40% reduction in estimated glomerular filtration rate eGFR, severe albuminuria, or kidney failure) and acute kidney injury (AKI). Secondary outcomes included the individual components of CKD, albuminuria, and death. Intention-to-treat effects were estimated using inverse probability of treatment weights, comparing risks for CKD assessed by the Aalen-Johansen estimator, and AKI burden by mean cumulative counts (MCCs; mean number of events per individual as multiple AKI events were possible). Subgroup analyses included stratification by preexisting cardiovascular or kidney disease. Results The study included 36 279 individuals who initiated an SGLT2i and 18 782 who initiated a GLP-1RA (median IQR age, 63 55-71 years vs 61 52-70 years), with comparable diabetes duration, eGFR, and urine albumin-creatinine ratios. The weighted 5-year risk of CKD was 6.7% (95% CI, 6.4%-7.0%) for SGLT2i initiators and 8.2% (95% CI, 7.8%-8.6%) for GLP-1RA initiators (risk ratio: 0.81 95% CI, 0.76-0.87; risk difference: −1.5% 95% CI, −2.0% to −1.0%). The 5-year MCC of AKI per 100 individuals was 25.2 (95% CI, 24.4-26.1) for SGLT2i initiators and 28.7 (95% CI, 27.4-30.0) for GLP-1RA initiators (MCC ratio: 0.88 95% CI, 0.83-0.93; MCC difference: −3.5 95% CI, −5.0 to −2.0). In contrast, the secondary outcomes of albuminuria and mortality were slightly reduced in GLP-1RA initiators. Results were consistent across subgroups, with the most pronounced CKD and AKI reductions with SGLT2i observed among individuals without preexisting kidney disease. Conclusions and Relevance This comparative effectiveness study found that initiation of SGLT2i vs GLP-1RA treatment in individuals with type 2 diabetes was associated with a lower 5-year risk of CKD and a lower 5-year count of AKI. These findings underscore the potential of SGLT2i treatment for primary prevention of kidney disease in individuals with type 2 diabetes.