Meta-Analysis of SGLT2 Inhibitors in Transthyretin Cardiac Amyloidosis: Insights by Disease-Modifying Therapy

Sodium glucose co-transporter 2 inhibitors (SGLT2i) improve outcomes in heart failure (HF), but evidence in transthyretin cardiac amyloidosis (ATTR-CM)-particularly in patients not receiving disease-modifying therapy (DMT)-remains limited.

This study aimed to evaluate the efficacy and safety of SGLT2i in ATTR-CM, stratified by DMT.

PubMed, Embase, and Cochrane were systematically searched for studies evaluating SGLT2i in ATTR-CM. Primary outcomes were all-cause mortality and HF hospitalization; secondary outcomes included safety events. Effect estimates were reported as HR or risk ratio with 95% CIs, with heterogeneity assessed by I².

Fourteen observational studies (10.852 patients) were analyzed; 5.453 patients received SGLT2i and 43.6% had diabetes. Of 7.708 patients (k = 12) with known DMT status, 34.6% received DMT. Follow-up ranged from 3 months to 5.5 years. Treatment with SGLT2i was associated with a lower risk of all-cause mortality (k = 6; n = 5.135; risk ratio: 0.44; P < 0.001; I² = 53.9%), although 2 studies reported zero events (k = 4; n = 5.038). Similarly, the risk of HF hospitalization was reduced (k = 2; n = 1.438; HR: 0.62; P < 0.001; I² = 0%). Subgroup analyses stratified by DMT and diabetes status showed a consistent direction of association, although these findings require further validation. The pooled prevalence of adverse events (k = 7; n = 535) was 7.28% (I² = 76.6%).

In observational studies, SGLT2i therapy in ATTR-CM is associated with lower all-cause mortality and HF hospitalizations. These findings are clinically encouraging, particularly for patients not receiving DMT, in whom therapeutic options remain limited. Prospective randomized trials are warranted to confirm these findings and better define SGLT2i benefit according to DMT.