Cardiovascular and Kidney Outcomes following Sodium-Glucose Cotransporter 2 Inhibitor Initiation in CKD: A Swedish Nationwide Cohort Study

KEY POINTS: In nationwide nephrology-referred CKD, sodium-glucose cotransporter 2 inhibitor use was associated with lower cardiovascular event and KRT risk. Associations with cardiovascular events and KRT were consistent in advanced CKD, a group underrepresented in trials. Findings supported the applicability of trial results to a broad nephrology-referred CKD population. BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) reduce cardiovascular (CV) and kidney events in randomized trials, yet evidence on their effectiveness in routine nephrology practice remains limited. We examined CV and kidney outcomes associated with SGLT2 inhibitor initiation in adults with CKD receiving specialist nephrology care. METHODS: In this nationwide cohort study, we included adults with CKD receiving specialist nephrology care, identified through the Swedish Renal Registry between January 1, 2016, and December 31, 2023. Participants had baseline data on eGFR, urine albumin-to-creatinine ratio, and hemoglobin; those with prior KRT were excluded. Follow-up continued until December 31, 2024. SGLT2 inhibitor use was identified through national pharmacy records and analyzed according to an intention-to-treat approach. Outcomes were major adverse cardiovascular events (MACE), initiation of KRT, all-cause mortality, and a composite of heart failure hospitalization or CV death. Associations were estimated using inverse probability-weighted marginal structural models to address time-dependent confounding. RESULTS: Among 32,856 participants (median age 73 years [interquartile range, 63-79]; 36% women; mean eGFR 29.3±16.8 ml/min per 1.73 m 2 ), 1493 (4.5%) were prevalent SGLT2 inhibitor users at baseline and 3491 (10.6%) initiated treatment during follow-up (4984 ever-exposed, 15.2%). SGLT2 inhibitor use was associated with a lower risk of MACE (odds ratio 0.80, 95% confidence interval, 0.71 to 0.91) and KRT (0.67, 0.52 to 0.85). No associations were observed for all-cause mortality (0.95, 0.79 to 1.15) or the composite heart failure outcome (0.87, 0.65 to 1.16), although a lower risk was observed in the incident-user analysis (0.61, 0.38 to 0.98). Associations were generally consistent across prespecified subgroups. CONCLUSIONS: In adults with CKD managed in specialist nephrology care, SGLT2 inhibitor use was associated with a lower risk of MACE and KRT, extending randomized trial evidence to a broad, real-world CKD population.