Abstract Body: Introduction:
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in cardiovascular-kidney-metabolic diseases, but the high-risk population of patients with transthyretin amyloid cardiomyopathy has been traditionally excluded from its trials (ATTR-CM). Tafamidis remains the only approved treatment, but its limited availability and high residual mortality demand alternative therapies. In light of recent studies, this meta-analysis aimed to investigate the effect of SGLT2i on the outcomes of patients with ATTR-CM.
Hypothesis:
SGLT2i might improve cardiovascular outcomes in patients with transthyretin amyloid cardiomyopathy.
Methods:
A comprehensive search of Medline, Google Scholar, Clinical trial registries, and the Cochrane Library was conducted up to October 2025. Study selection and data extraction were carried out independently by two investigators. Associations of SGLT2i with outcomes were pooled using random-effects meta-analyses.
Results:
A total of eight studies (8451 participants, six propensity score-matched) were included. The use of SGLT2i was associated with significant reductions in all-cause mortality [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.34-0.7], cardiovascular mortality (HR 0.39, 95% CI 0.23-0.65), and heart failure hospitalizations (HFHs) (HR 0.64, 95% CI 0.54- 0.76) compared to non-use. SGLT2i preserved renal function by significant attenuation of decline in estimated GFR (MD: 3.34 ml/min/1.73 mm2, 95% CI: 0.75, 5.94). SGLT2i also reduced cardiac wall stress with attenuation of the increase in pro B BNP levels (MD: -424.48 from baseline compared to control, 05% CI: -803.54, -45.41).
Conclusions:
The use of SGLT2 may confer cardiorenal protection in patients with ATTR-CM with significant potential to reduce morbidity and healthcare utilization. These findings highlight SGLT2i as a viable adjunct to existing therapies like tafamidis and warrant further investigation through adequately powered, long-term RCTs randomized trials.