Mortality and heart failure benefits of sglt2 inhibitors in transthyretin amyloid cardiomyopathy: a cohort and integrated meta-analysis

Background

The evidence supporting sodium–glucose cotransporter-2 inhibitors (SGLT2i) in heart failure (HF) secondary to transthyretin amyloid cardiomyopathy (ATTR-CM) remains scarce and fragmented across small observational series.

Purpose

To evaluate the impact of SGLT2i on clinical outcomes in ATTR-CM through a single-center cohort study, integrating results into a meta-analysis of available evidence.

Methods

A retrospective cohort of patients with ATTR-CM (2014–2024, n=111) was analyzed, comparing those treated with SGLT2i versus non-treated. The primary endpoint was all-cause mortality (ACM); secondary endpoints included heart failure hospitalizations (HFH) and the composite of ACM and HFH. A time-varying treatment exposure Cox regression, adjusted for 12 baseline covariates, was used to account for confounding and immortal-time bias. A systematic search of CENTRAL, Scopus, EMBASE, and PubMed (October 10, 2025) identified studies evaluating SGLT2i effects on outcomes of interest in ATTR-CM. Hazard ratios (HRs) were extracted or converted from relative risks, prioritizing covariate-adjusted or propensity-matched estimates. Data were pooled using inverse-variance random-effects meta-analyses to estimate overall effects.

Results

In the institutional cohort, time-varying analysis demonstrated lower ACM among SGLT2i users (HR 0.35, 95% CI 0.13–0.97; p=0.04) over a median 25-month follow-up (IQR 16–39). Rates of HFH and the composite outcome did not differ significantly between patients treated with SGLT2i and those not receiving SGLT2i therapy.

The meta-analysis pooled data from 4 observational studies and the institutional cohort (n= 5909). SGLT2i use was associated with reduced ACM (pooled HR 0.56, 95% CI 0.46–0.68; I² = 24%), fewer HFH (HR 0.66, 95% CI 0.51–0.86; I² = 30%), and lower risk of the composite outcome (HR 0.55, 95% CI 0.38–0.80; I² = 0%). No significant heterogeneity or small-study effects were detected.

Conclusions

SGLT2i therapy in transthyretin amyloid cardiomyopathy (ATTR-CM) was associated with significant reductions in ACM and HFH in pooled analyses, consistent with findings from the institutional cohort. These results support the emerging role of SGLT2i as a potentially disease-modifying adjunct in the management of ATTR-CM and highlight the need for confirmation in prospective randomized trials.For image description, please refer to the figure legend and surrounding text.