Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Primary Aldosteronism

Background: Patients with primary aldosteronism (PA) are at increased risk of cardiovascular and kidney complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated protective effects in individuals at high risk for cardiorenal events. This study investigates whether adding SGLT2 inhibitors to mineralocorticoid receptor antagonists (MRA) associates with better outcomes in patients with PA. Methods: We retrospectively analyzed TriNetX data (Feb 1, 2014–Feb 1, 2025) using an incident cohort design in adults with PA treated with MRAs within three months before or after PA diagnosis, excluding those who underwent adrenalectomy. Patients were divided into two cohorts based on initiation of an SGLT2 inhibitor within three months of the PA diagnosis. The primary outcome was three-year all-cause mortality; secondary outcomes included major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE). We performed 1:1 propensity score matching (PSM) and estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox proportional hazards models. Results: A total of 24,074 patients with PA were included; 34% had comorbid diabetes, 26% had heart failure, and 2,524 (11%) received SGLT2 inhibitors. After a well-balanced PSM, 2,507 SGLT2 inhibitor users were compared with 2,507 non-users. In the matched cohort, the incidence of all-cause mortality was 12% in SGLT2i users and 18% in non-users. The combination of SGLT2 inhibitor with MRA was associated with a lower risk of all-cause mortality (aHR, 0.59; 95% CI, 0.51–0.68; absolute risk reduction [ARR], 7%), MACE (aHR, 0.81; 95% CI, 0.69–0.94; ARR, 3%), and MAKE (aHR, 0.58; 95% CI, 0.52–0.65; ARR, 10%). Kaplan–Meier survival curves for all outcomes demonstrated early divergence and remained distinct through the three-year follow-up period. Conclusions: In patients with PA, adding SGLT2 inhibitors to MRAs is associated with lower mortality and cardiorenal complications. These associations offer a rationale for evaluation of this combined strategy to improve long-term outcomes in this high-risk population.