Comparative Effectiveness of GLP-1 Receptor Agonists in Patients with Heart Failure with Preserved or Minimally Reduced Ejection Fraction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Authors

Ibrahim Khalil
M. Rafiqul Islam
A.B.M. Kamrul-Hasan
Lakshmi Nagendra
Sunjida Amin Promi
Md Abu Sayed
Mohd Turzo Rahman
Norwin Sultana
Noshin Anjum Tasmi
Manisha Das
Salsabil Tarannum
Rajendronath Dey
Deep Dutta
Pallab Sarker, Department of Medicine, Division of Internal Medicine, Reading Hospital - Tower Health, West Reading, PAFollow

Document Type

Abstract

Publication Date

12-1-2025

Abstract

Introduction: Heart failure with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF) remains difficult to manage, especially in patients with type 2 diabetes (T2D) or obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are emerging therapies, but their comparative effectiveness is unclear. Methods: A Bayesian network meta-analysis (NMA) of six randomized controlled trials (RCTs) involving 24,099 patients was conducted. Systematic searches were performed across PubMed, Embase, Scopus, and Cochrane Library databases with maintaining PRISMA flowchart. Analyses used R (v4.4.3) with random-effects model selected by deviance-information criterion (DIC). Effect sizes included hazard ratios (HR) for time-to-event outcomes and mean differences (MD) for continuous outcomes. Treatment ranking was evaluated using Surface Under the Cumulative Ranking Curve (SUCRA). Results: Semaglutide significantly reduced hospitalization for heart failure [HHF], (HR: 0.52, 95%, CrI [0.25, 0.87]); [Fig-1] and worsening HF events (HR: 0.33, 95%, CrI [0.13, 0.68]). It also improved 6-minute walk distance (MD: +17.09 meters, SUCRA: 75.9%); [Fig-3] and reduced body weight (MD: -8.35%, SUCRA: 60.8%); [Fig-5]. Tirzepatide demonstrated the greatest weight reduction (MD: -12.07%, SUCRA: 87.9%) and ranked highest for HHF reduction (SUCRA: 76.9%). Exenatide had the best ranking for all-cause mortality (HR: 0.73, SUCRA: 86.9%); [Fig-4] while semaglutide ranked best for cardiovascular mortality (HR: 0.83, SUCRA: 75.1%); [Fig-2]. Conclusion: Semaglutide and tirzepatide offer superior outcomes for patients with HFpEF/HFmrEF. Semaglutide improves cardiovascular and functional endpoints, while tirzepatide provides the greatest weight loss. These therapies may significantly enhance care for patients with coexisting obesity or T2D.

Publication Title

American Heart Journal

Volume

290

Issue

Supplement

First Page

20

Last Page

20

Comments

9th Heart in Diabetes Conference held 2025-06-06 to 2025-06-08 in Philadelphia, PA, USA.

Recommended Citation

Khalil, I., Islam, M., Kamrul-Hasan, A., Nagendra, L., Promi, S. A., Sayed, M. A., Rahman, M. T., Sultana, N., Tasmi, N. A., Das, M., Tarannum, S., Dey, R., Dutta, D., & Sarker, P. (2025). Comparative Effectiveness of GLP-1 Receptor Agonists in Patients with Heart Failure with Preserved or Minimally Reduced Ejection Fraction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. American Heart Journal, 290 (Supplement), 20-20. https://doi.org/https://doi.org/10.1016/j.ahj.2025.07.049