Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus

<jats:sec id="ab-zoi240547-4"><jats:title>Importance</jats:title><jats:p>Lupus nephritis is a major complication of systemic lupus erythematosus (SLE). Randomized clinical trials have shown nephroprotective and cardioprotective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is).</jats:p></jats:sec><jats:sec id="ab-zoi240547-5"><jats:title>Objective</jats:title><jats:p>To investigate whether the use of SGLT2is is associated with the onset and progression of lupus nephritis and other kidney and cardiac outcomes in patients with SLE and type 2 diabetes.</jats:p></jats:sec><jats:sec id="ab-zoi240547-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This multicenter cohort study used the US Collaborative Network of the TriNetX clinical data platform to identify patients with SLE and type 2 diabetes from January 1, 2015, to December 31, 2022. Data collection and analysis were conducted in September 2023.</jats:p></jats:sec><jats:sec id="ab-zoi240547-7"><jats:title>Exposures</jats:title><jats:p>Individuals were categorized into 2 groups by SGLT2i use or nonuse with 1:1 propensity score matching.</jats:p></jats:sec><jats:sec id="ab-zoi240547-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The Kaplan-Meier method and Cox proportional hazards regression models were used to calculate the 5-year adjusted hazard ratios (AHRs) of lupus nephritis, dialysis, kidney transplant, heart failure, and mortality for the 2 groups.</jats:p></jats:sec><jats:sec id="ab-zoi240547-9"><jats:title>Results</jats:title><jats:p>From 31 790 eligible participants, 1775 matched pairs of SGLT2i users and nonusers (N = 3550) were selected based on propensity scores. The mean (SD) age of matched participants was 56.8 (11.6) years, and 3012 (84.8%) were women. SGLT2i users had a significantly lower risk of lupus nephritis (AHR, 0.55; 95% CI, 0.40-0.77), dialysis (AHR, 0.29; 95% CI, 0.17-0.48), kidney transplant (AHR, 0.14; 95% CI, 0.03-0.62), heart failure (AHR, 0.65; 95% CI, 0.53-0.78), and all-cause mortality (AHR, 0.35; 95% CI, 0.26-0.47) than SGLT2i nonusers.</jats:p></jats:sec><jats:sec id="ab-zoi240547-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this cohort study of patients with SLE and type 2 diabetes, SGLT2i users had a significantly lower risk of lupus nephritis, dialysis, kidney transplant, heart failure, and all-cause mortality than nonusers. The findings suggest that SGLT2is may provide some nephroprotective and cardioprotective benefits.</jats:p></jats:sec>