Role SGLT2 inhibitor therapy in patients with transthyretin cardiac amyloidosis: a GRADE assessed systematic review and meta-analysis.

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, p < 0.00001; I2 = 10%), cardiovascular mortality (RR: 0.30 [0.16, 0.55] 95% CI; p = 0.0001; I2 = 25%) and MACE (RR: 0.69 [0.59, 0.81] 95% CI; p < 0.00001; I2 = 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, p = 0.02; I2 = 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.