Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Primary Aldosteronism.

key pointsPrimary aldosteronism patients on mineralocorticoid receptor antagonists face high cardio-renal risks, but evidence for effective add-on therapies remains limited. Adding sodium-glucose cotransporter 2 inhibitors to mineralocorticoid receptor antagonists reduced 3-year mortality by 6.6%, major adverse cardiovascular events by 2.7%, and major adverse kidney events by 9.7% absolute risk. Mineralocorticoid receptor antagonist-sodium-glucose cotransporter 2 inhibitor combination therapy offers a promising strategy to improve long-term survival and organ preservation in primary aldosteronism.

backgroundPatients with primary aldosteronism (PA) are at an increased risk of cardiovascular and kidney complications. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated protective effects in individuals at a high risk of cardiorenal events. This study investigates whether adding SGLT2is to mineralocorticoid receptor antagonists (MRAs) associates with better outcomes in patients with PA.

methodsWe retrospectively analyzed TriNetX data (February 1, 2014 to February 1, 2025) using an incident cohort design in adults with PA treated with MRAs within 3 months before or after PA diagnosis, excluding those who underwent adrenalectomy. Patients were divided into two cohorts based on initiation of an SGLT2i within 3 months of the PA diagnosis. The primary outcome was 3-year all-cause mortality; secondary outcomes included major adverse cardiovascular events and major adverse kidney events. We performed 1:1 propensity score matching and estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox proportional hazards models.

resultsA total of 24,074 patients with PA were included; 34% had comorbid diabetes, 26% had heart failure, and 2524 (11%) received SGLT2is. After a well-balanced propensity score matching, 2507 SGLT2i users were compared with 2507 nonusers. In the matched cohort, the incidence of all-cause mortality was 12% in SGLT2i users and 18% in nonusers. The combination of SGLT2i with MRA was associated with a lower risk of all-cause mortality (aHR, 0.59; 95% CI, 0.51 to 0.68; absolute risk reduction [ARR], 7%), major adverse cardiovascular event (aHR, 0.81; 95% CI, 0.69 to 0.94; ARR, 3%), and major adverse kidney event (aHR, 0.58; 95% CI, 0.52 to 0.65; ARR, 10%). Kaplan-Meier survival curves for all outcomes demonstrated early divergence and remained distinct through the 3-year follow-up period.

conclusionsIn patients with PA, adding SGLT2is 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.