Tolerability and efficacy of sodium-glucose co-transporter 2 inhibitors in patients with cardiac amyloidosis: a meta-analysis of observational studies

Aims: The role of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with cardiac amyloidosis (CA) is controversial. However, they have shown encouraging results in several clinical settings, including heart failure, myocardial infarction, chronic kidney disease, and various forms of restrictive cardiomyopathy. The current study aims to evaluate the tolerability and efficacy of SGLT2i in patients with CA.

Methods and results: PubMed, Scopus, Cochrane Library, and Embase were scanned for eligible articles up to 28th of March 2025. Safety endpoints included the cumulative prevalence of adverse events (AEs) and drug discontinuation (DD) in the SGLT2i-group. Efficacy endpoints were the pooled risk ratio (RR) of all-cause death (ACD) and hospitalization due to worsening heart failure (WHF) between treatment- and control-groups, as well as the difference between mean change of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in both treatment- and control-groups. Thirteen observational studies, encompassing 19 227 patients, were included in the meta-analysis. Sodium-glucose co-transporter 2 inhibitors use in patients with CA resulted to be tolerable, as demonstrated by a low absolute cumulative prevalence of both AEs [8%; 95% confidence interval (CI) 2-17, nine studies, 603 patients] and DD (4%; 95% CI: 1-7, nine studies, 603 patients). Furthermore, its use was associated with a reduction in the risk of ACD (RR 0.59; 95% CI: 0.48-0.72) and NT-proBNP levels (median difference: -525.54; 95% CI: -718.09 to -332.98), despite no significant association with WHF was noted.

Conclusion: The administration of SGLT2i proved to be well tolerated in patients with CA. Randomized controlled trials are urgently needed to confirm the prognostic improvement associated with their use in this clinical setting.

Study registration: CRD42025632733.