AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
SGLT2 Inhibition in Pericarditis: Pericardial and Mortality Outcomes in Type 2 Diabetes
By El Dahdah J, Vignarajah A, Klein AL
Background: Pericarditis is driven by NLRP3 inflammasome activation and interleukin-1β release. SGLT2 inhibitors (SGLT2i) attenuate NLRP3 inflammasome activity and exert anti-inflammatory effects, yet their impact on pericardial disease outcomes is unknown. Methods: Using the TriNetX federated research network (44 healthcare organizations), we identified adults with type 2 diabetes (ICD-10 E11) and pericarditis - acute or chronic (I30, I30.0, I30.8, I31, I31.0, I31.1) - diagnosed 2006-2026, excluding infective (I30.1), malignant (I31.31), and post-pericardiectomy (CPT 33030/33031) etiologies. Patients receiving anakinra, rilonacept, GLP-1 receptor agonists, or with type 1 diabetes (E10) were excluded. Cohort 1 received an SGLT2i (dapagliflozin, empagliflozin, canagliflozin, or ertugliflozin) after pericarditis diagnosis; Cohort 2 did not. Propensity score matching (1:1) balanced 67 covariates spanning demographics, comorbidities, medications, and laboratory values. Outcomes from day 42-1,095 post-index were recurrent pericarditis; pericardial complications (effusion I31.3, tamponade I31.4, myocarditis I41, constrictive pericarditis I31.1); and all-cause mortality. Hazard ratios (HR) were estimated using a proportional hazards model. Results: After matching, 5,782 patients per cohort were analyzed for recurrent pericarditis and pericardial complications; the mortality analysis included 5,590 SGLT2i and 5,282 non-SGLT2i patients after excluding deaths preceding the outcome window. Cohorts were well balanced, including age at index (63.4 vs 63.4 years; P = 0.86) and female sex (44.6% vs 44.3%; P = 0.79). SGLT2i use was associated with a 47% lower rate of recurrent pericarditis (HR, 0.53; 95% CI, 0.43-0.66; P < 0.001), a 30% lower rate of pericardial complications (HR, 0.70; 95% CI, 0.64-0.78; P < 0.001), and a 33% lower rate of all-cause mortality (HR, 0.67; 95% CI, 0.61-0.73; P < 0.001). Conclusions: In this propensity score-matched cohort of patients with type 2 diabetes and pericarditis, SGLT2i use was associated with lower rates of recurrent pericarditis, pericardial complications, and mortality. These findings support the hypothesis that SGLT2i-mediated NLRP3 inflammasome suppression may confer therapeutic benefit in pericardial disease and warrant prospective investigation.