Clinical journal of the American Society of Nephrology : CJASN · 2026
Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Primary Aldosteronism.
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Chang Li-Yang, Huang Chieh, Su Ching-Chun, Tsai Cheng-Hsuan, Wu Che-Hsiung, Lai Chun-Fu, Wu Vin-Cent, Taiwan Primary Aldosteronism Investigation (TAIPAI) study group
Аннотация
KEY POINTS: Primary 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.
BACKGROUND: Patients 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.
METHODS: We 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.
RESULTS: A 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.
CONCLUSIONS: In 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.
BACKGROUND: Patients 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.
METHODS: We 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.
RESULTS: A 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.
CONCLUSIONS: In 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.