Meta-Analysis of SGLT2 Inhibitors in Transthyretin Cardiac Amyloidosis
6 affiliations
- 1Department of Cardiology, Cardiovascular Research Institute Maastricht, University of Maastricht & Maastricht University Medical Center, Maastricht, The Netherlands
- 2Department of Clinical, Internal, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
- 3Department of Hospital Therapy, Uzhhorod National University, Uzhhorod, Ukraine
- 4Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, IRCCS Italian Cardiology Network, Genova, Italy
- 5Department of Internal Medicine, University of Genova, Genova, Italy
- 6Department of Clinical and Experimental Medicine, Cardiology Unit, University of Messina, Messina, Italy
Abstract
Background: 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. Objectives: This study aimed to evaluate the efficacy and safety of SGLT2i in ATTR-CM, stratified by DMT. Methods: 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 I 2 . Results: 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; I 2 = 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; I 2 = 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% (I 2 = 76.6%). Conclusions: 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.
Related
- Effect of Transthyretin Stabilizer in Transthyretin Cardiac Amyloidosis
- Gender and Racial Distribution of Transthyretin Stabilizer Therapy in Patients With Transthyretin Cardiac Amyloidosis.
- A Progressive 99mTc-MDP Uptake in Transthyretin Cardiac Amyloidosis
- The Progressive Cardiac Uptake of 99mTc-MDP as a Clue to Transthyretin Amyloidosis
- Transcatheter Mitral Edge-to-edge Repair in Patients with Transthyretin Cardiac Amyloidosis: A Four-case Series
BibTeX
@article{lorenzobianchi2026metaanalysis,
title = {{Meta-Analysis of SGLT2 Inhibitors in Transthyretin Cardiac Amyloidosis}},
author = {Lorenzo Bianchi, MD and Giulia Marchionni, MD and Taras Chendey, MD and Stefano Benenati, MD and Andrea Minghini, MD and Federico Giannino, MD and Giulia Cavolina, MD and Camilla Soragni, PhD and Cristina Chimenti, MD, PhD},
journal = {JACC: Advances},
year = {2026},
month = jul,
doi = {10.1016/j.jacadv.2026.102972},
url = {https://doi.org/10.1016/j.jacadv.2026.102972},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Meta-Analysis of SGLT2 Inhibitors in Transthyretin Cardiac Amyloidosis
AU - Lorenzo Bianchi, MD
AU - Giulia Marchionni, MD
AU - Taras Chendey, MD
AU - Stefano Benenati, MD
AU - Andrea Minghini, MD
AU - Federico Giannino, MD
AU - Giulia Cavolina, MD
AU - Camilla Soragni, PhD
AU - Cristina Chimenti, MD, PhD
PY - 2026
DA - 2026/07/22
JO - JACC: Advances
DO - 10.1016/j.jacadv.2026.102972
UR - https://doi.org/10.1016/j.jacadv.2026.102972
AB - Background: 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. Objectives: This study aimed to evaluate the efficacy and safety of SGLT2i in ATTR-CM, stratified by DMT. Methods: 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 I 2 . Results: 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; I 2 = 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; I 2 = 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% (I 2 = 76.6%). Conclusions: 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.
SN - 2772-963X
ER -