New horizons in transthyretin cardiac amyloidosis therapy: A systematic review and meta-analysis of sodium-glucose cotransporter 2 inhibitors efficacy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) has historically been underdiagnosed, but recent advances in diagnostic techniques and heightened clinical awareness have led to a significant increase in its detection. Despite this progress, treatment options remain limited, as current FDA-approved therapies are costly and not widely accessible. Given the promising benefits of SGLT2 inhibitors observed in broader heart failure (HF) populations, our objective was to systematically evaluate their efficacy in reducing mortality and hospitalizations in patients with ATTR-CM. Methods We performed a systematic review and meta-analysis of SGLT2 inhibitors against SGLT2 inhibitors-naïve in patients with ATTR-CM. PubMed, Embase, Scopus and Cochrane databases were searched for trials published up to January 31, 2025. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. Risk ratios (RRs) with 95% CI were pooled across trials. Outcomes included all-cause mortality, cardiovascular (CV) mortality and HF hospitalization. Results Out of 177 database results, 04 observational studies and 5039 patients were included; 2489 (49.39%) received a SGLT2 inhibitor. All-cause mortality (RR 0.44; 95% CI 0.33-0.59; p0.00001; I²=54%) and CV mortality (RR 0.30; 95% CI 0.16-0.55; p=0.0001; I²=25%) were significantly lower in patients treated with SGLT2 inhibitors compared with control. HF hospitalization (RR 0.68; 95% CI 0.33-1.41; p=0.30; I²=89%) showed a downward trend, yet this was not statistically significant. Conclusions In patients with ATTR-CM, SGLT2 inhibitors significantly reduce both all-cause and cardiovascular mortality compared to standard care. Although a downward trend in HF hospitalizations was observed, it did not reach statistical significance. Further randomized controlled trials are needed to confirm these promising findings.