Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) in Cardiac Amyloidosis: A Systematic Review.

INTRODUCTION

Cardiac amyloidosis is an underdiagnosed cause of heart failure characterized by extracellular deposition of misfolded proteins, most commonly transthyretin (ATTR) or immunoglobulin light chains (AL). Despite recent advances in disease-modifying therapies, prognosis remains poor. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular and renal benefits. However, evidence regarding their safety and efficacy in cardiac amyloidosis remains limited.

AIM: This systematic review aimed to synthesize current evidence on the clinical outcomes and safety of SGLT2 inhibitors in patients with cardiac amyloidosis.

METHODS

A comprehensive literature search was conducted in PubMed, Embase, Google Scholar, ScienceDirect, and Cochrane Library through June 2025, in accordance with PRISMA guidelines. Studies evaluating the use of SGLT2i in cardiac amyloidosis were included. Outcomes assessed were all-cause mortality, stroke, hospitalization for heart failure, and kidney failure. Data extraction and quality assessment were performed independently by two reviewers. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled when appropriate.

RESULTS

Five studies comprising 17,416 patients met inclusion criteria. The mean age was 76.8 years, and 78% were male. Use of SGLT2 inhibitors was associated with a significant reduction in all-cause mortality (HR 0.64; 95% CI 0.57-0.71) and stroke risk (HR 0.64; 95% CI 0.54-0.77). For hospitalization due to heart failure, there was a trend toward benefit (HR 0.88; 95% CI 0.76-1.02), though this did not reach statistical significance. The risk of kidney failure was modestly reduced (HR 0.91; 95% CI 0.71-1.08). Overall study quality was moderate.

CONCLUSIONS

SGLT2 inhibitors appear to be a promising therapeutic option in cardiac amyloidosis, potentially improving survival and reducing cerebrovascular events while maintaining a favorable safety profile. However, current evidence is limited by observational study designs and heterogeneity. High-quality randomized controlled trials are needed to confirm these findings and guide clinical practice.