Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Mar;25(2):231-240.
doi: 10.1007/s40256-024-00697-7. Epub 2024 Dec 2.

A Systematic Review and Meta-Analysis of the Safety and Efficacy of SGLT2 Inhibitors in Chronic Heart Failure in ACHD Patients

Bibhuti B Das  1 , Jianli Niu  2
Affiliations
Meta-Analysis

A Systematic Review and Meta-Analysis of the Safety and Efficacy of SGLT2 Inhibitors in Chronic Heart Failure in ACHD Patients

Bibhuti B Das et al. Am J Cardiovasc Drugs. 2025 Mar.

Abstract

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have become a first-line therapy for heart failure (HF) in adults. However, data on their use in HF associated with adult congenital heart disease (ACHD) are limited. This systematic review and meta-analysis evaluated the safety, tolerability, and efficacy of SGLT2is in ACHD HF patients, supplementing guideline-directed medical therapy.

Methods: A comprehensive systematic search and meta-analysis were conducted on studies examining SGLT2i use in ACHD HF patients. The primary endpoint was the change in the New York Heart Association (NYHA) functional class (FC), with secondary endpoints including changes in ventricular function and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Additionally, the safety and tolerability of SGLT2is were evaluated.

Results: The meta-analysis included eight studies with 287 patients aged 19-67 years (median age 37.5 years). Adding SGLT2is to combined therapies significantly improved NYHA FC (log odds ratio 1.3, 95% confidence interval [CI] 0.37-2.23, p = 0.01) and reduced NT-proBNP levels (mean difference [MD] -0.43, 95% CI -0.70 to -0.16, p < 0.001). A notable decrease in systolic blood pressure was observed (MD -0.32, 95% CI -0.51 to -0.14, p = 0.00). The adverse effect profile was comparable to that seen in routine HF, with fewer HF hospitalizations post-SGLT2i initiation. Urinary tract infections occurred in 14 patients (5%), with no instances of hypoglycemia or ketoacidosis reported. Medication withdrawal due to adverse effects was noted in 19 patients (7%).

Conclusions: SGLT2is are well tolerated in ACHD HF patients. Notably, SGLT2is improved NYHA FC and reduced NT-proBNP levels across a diverse ACHD HF patient cohort. However, further prospective, multicenter studies are needed to confirm the safety and efficacy of SGLT2is in this unique patient population.

PubMed Disclaimer

Conflict of interest statement

Declarations. Funding: No external funding was used in the preparation of this article. Conflict of Interest: Bibhuti B. Das and Jianli Niu declare that they have no potential conflicts of interest that might be relevant to the contents of this article. Ethics Approval: Not applicable. Code Availability: Not applicable Consent to Participate: Not applicable. Consent for Publication: Not applicable. Data Availability: All the data generated or analyzed during this study are included in this published article (and its supplementary information files). Authors' Contributions: BD: Conceptualization, data curation, methodology, project administration, writing, reviewing, and editing. JN: Data curation, statistical analysis, reviewing, revising, and editing.

Figures

Fig. 1
Fig. 1
Selection of studies on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. HF heart failure
Fig. 2
Fig. 2
Bar diagram summarizing the percentage of patients receiving each drug for HF in each study. ACEi angiotensin-converting enzyme inhibitor, ACHD adult congenital heart disease, ARB angiotensin receptor blocker, ARNI angiotensin receptor–neprilysin inhibitor, BB β-blocker, HF heart failure, MRA mineralocorticoid receptor antagonist, SGLT2is sodium–glucose cotransporter 2 inhibitors
Fig. 3
Fig. 3
A Improvement in the NYHA functional class, B decrease in NT-proBNP, C decrease in the systolic blood pressure, and D no significant change in the serum creatinine level. CI confidence interval, MD mean difference, NYHA New York Heart Association, NT-proBNP N-terminal pro B-type natriuretic peptide, OR odds ratio, SGLT2i sodium–glucose cotransporter 2 inhibitor
See this image and copyright information in PMC

References

    1. Burstein DS, Rossano JW, Griffis H, Zhang X, Fowler R, Frischertz B, Kim YY, Lindenfield J, Mazurek JA, Edelson JB, et al. Greater admissions, mortality and cost of heart failure in adults with congenital heart disease. Heart. 2021;107(10):807–13. 10.1136/heartjnl-2020-318246. - PubMed
    1. Egbe AC, Miranda WR, Jain CC, Stephens EH, Andi K, Abozied O, Connolly HM. Temporal changes in clinical characteristics and outcomes of adults with congenital heart disease. Am Heart J. 2023;264:1–9. 10.1016/j.ahj.2023.05.025. - PMC - PubMed
    1. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, et al. AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation. 2022. 10.1161/cir.0000000000001063. - PubMed
    1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, et al. 2023 Focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail. 2024;26(1):5–17. 10.1002/ejhf.3024. - PubMed
    1. Solomon SD, Jhund PS, Claggett BL, Dewan P, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Inzucchi SE, et al. Effect of dapagliflozin in patients with HFrEF treated with sacubitril/valsartan. JACC Heart Fail. 2020;8(10):811–8. 10.1016/j.jchf.2020.04.008. - PubMed

Substances