Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Amyloidosis With or Without Heart Failure

Abstract

Background: Emerging evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefits may extend to patients with amyloid cardiomyopathy, including transthyretin and amyloid light-chain amyloidosis subtypes. This study explores the broader implications of SGLT2i therapy across the spectrum of amyloidosis.

Methods: This retrospective cohort study used de-identified electronic health records from the TriNetX platform, encompassing data from 101 healthcare organizations between 2009 and 2024. Two cohorts of amyloidosis patients with heart failure were compared based on SGLT2i use. One cohort without a diagnosis of heart failure was also tested. Propensity score matching was applied to balance baseline characteristics. The primary outcome was all-cause mortality, and secondary outcomes included acute heart failure, acute myocardial infarction, stroke, and chronic kidney disease.

Results: The matched cohorts included 5612 patients, with a mean age of 74 years and 64% male. SGLT2i-treated patients exhibited a higher 5-year survival probability (62.6%) compared to non-SGLT2i patients (39.1%) (HR: 0.54, 95% CI: 0.50-0.59; P < .001). In amyloidosis patients without heart failure (n = 1490), SGLT2i therapy was associated with a significant reduction in all-cause mortality (HR: 0.57, 95% CI: 0.43-0.74; P < .001). Sub-cohorts of transthyretin and amyloid light-chain amyloidosis in heart failure patients demonstrated consistent benefits with reduced mortality and favorable trends for acute myocardial infarction and stroke.

Conclusions: SGLT2i therapy is associated with significant survival benefits in amyloidosis patients with HF and may offer broader advantages across the amyloidosis spectrum, including amyloid patients without heart failure.

Keywords: Amyloid light-chain amyloidosis; Amyloidosis; Heart failure; SGLT2 inhibitors; Transthyretin amyloidosis.

Figure 1.. STROBE diagram.

Created in BioRender.

Figure 2.. SGLT2i treatment improves survival and reduces the risk of mortality

Kaplan-Meier curves comparing survival probabilities between cohorts during the 5-year follow-up. SGLT2i medication cohort had a higher survival probability for all-cause mortality in the main cohort of patients with diagnosis of amyloidosis (Figure 2A), in the cohort of patients with diagnosis of amyloidosis without heart failure (Figure 2B), as well as in the transthyretin amyloid (Figure 2C) and amyloid light chain (Figure 2D) sub-cohorts.