Impact of SGLT2 inhibitors in cardiac amyloidosis: A systematic review and meta-analysis.

Authors

Shreyas Nandyal, Aviral Vij, Revati Varma, Rohan Gajjar, Angelo Caputi, Samuel Odoi, Sukriti Banthiya, Saketh Vinjamuri, Saurabh Malhotra

Published in

American heart journal plus : cardiology research and practice. Volume 68. Pages 100822. Epub Jul 06, 2026.

Abstract

Cardiac amyloidosis (CA), including transthyretin (ATTR) and light-chain (AL) subtypes, is an underrecognized mimic of heart failure with preserved ejection fraction. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) benefit general heart failure (HF) populations, their role in CA is unclear. This study evaluated the impact of SGLT2i on outcomes in patients with CA.
A systematic review and meta-analysis of seven observational studies (N = 13,303) compared patients with CA (AL and ATTR) receiving SGLT2i to matched controls. Outcomes included mortality, HF exacerbations, estimated GFR (eGFR), and NT-proBNP. Random-effects models were used to pool hazard ratios (HRs) and mean differences.
In the primary analysis restricted to ATTR-CA, SGLT2i use was associated with lower observed all-cause mortality (the primary outcome; HR 0.71, 95% CI 0.58-0.87, p = 0.001). Among secondary outcomes in the ATTR-CA subgroup, SGLT2i use was associated with reduced NT-proBNP (-414 pg/mL, 95% CI -694 to -134, p = 0.004) and improved eGFR (+4.3 mL/min/1.73 m², 95% CI 1.4 to 7.2, p = 0.004). In a secondary, exploratory any-CA (AL + ATTR combined, 4 studies) analysis, the pooled mortality HR was 0.67 (95% CI 0.50-0.91, p = 0.010); between-study heterogeneity was substantial (I² = 75%), and this combined estimate should not be interpreted as a single class effect across CA subtypes.
In this meta-analysis of non-randomized observational studies, SGLT2 inhibitor use was associated with lower observed mortality and improved cardiac biomarkers in CA, with renal benefits most evident in ATTR. Because all included studies were observational and susceptible to confounding by indication, immortal time bias, and survivor bias, these findings are hypothesis-generating and should not be interpreted as evidence of efficacy; randomized trials are needed before treatment recommendations can be made.

PMID:
42437182
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.

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