SGLT2 inhibitors associated with lower mortality in ATTR-CM patients receiving disease-modifying therapy

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) patients continue to experience worsening heart failure despite therapy with disease modifying therapies (tafamidis, patisiran, etc.). Given the proven benefits of SGLT2 inhibitors in heart failure, their efficacy in ATTR-CM patients remains unexplored. METHODS: A systematic search of PubMed, Google Scholar, Web of Science, and Cochrane Central Library was conducted from inception to April 2025 for studies evaluating the efficacy of SGLT2 inhibitors in ATTR-CM patients receiving disease-modifying therapy. A random-effects meta-analysis model was used, and all-cause mortality was analysed as the primary outcome. RESULTS: Seven observational studies comprising 7283 patients with transthyretin amyloidosis (ATTR) cardiomyopathy were included. SGLT2 inhibitors were associated with lower risk of all-cause mortality (RR: 0.51 [0.45, 0.57] 95% CI,  < 0.00001;  = 10%), cardiovascular mortality (RR: 0.30 [0.16, 0.55] 95% CI;  = 0.0001;  = 25%) and MACE (RR: 0.69 [0.59, 0.81] 95% CI;  < 0.00001;  = 10%) as compared to patients receiving no SGLT2 inhibitor. Additionally, the use of SGLT2 inhibitors was associated with significantly improved glomerular filtration rates (MD: 3.11 [0.52, 5.71] 95% CI,  = 0.02;  = 54%) as compared to patients receiving no SGLT2 inhibitor. SGLT2 inhibitor therapy did not have a significant effect on the risk of hospitalisations due to heart failure. CONCLUSIONS: SGLT2 inhibitors, when used alongside disease-modifying agents, appear to improve survival and renal outcomes in patients with ATTR-CM. However, these findings are derived from observational studies with their inherent biases and must be interpreted with caution. High-quality randomised controlled trials are needed to confirm these associations and better define their clinical role in ATTR-CM.