Semaglutide in patients with obesity and heart failure with preserved ejection fraction: A systematic review and meta-analysis

doi:10.4330/wjc.v18.i3.112189

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World Journal of Cardiology

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World J Cardiol. Mar 26, 2026; 18(3): 112189
Published online Mar 26, 2026. doi: 10.4330/wjc.v18.i3.112189

Semaglutide in patients with obesity and heart failure with preserved ejection fraction: A systematic review and meta-analysis

Maneeth Mylavarapu, Ogechukwu Obi, Yozahandy Abarca, Husna Fatima, Prarath Roshni, Noor Ul Huda, Yuliya Lysak, Asad Gandapur, Samantha Contreras Vazquez, Muhammad Areeb Siddiqui, Adetola Mowo-Wale

Maneeth Mylavarapu, Department of Cardiology, Endeavor Health Cardiovascular Institute, Glenview, IL 60026, United States

Ogechukwu Obi, Department of Internal Medicine, New York Institute of Technology: College of Osteopathic Medicine, Westbury, NY 11568, United States

Yozahandy Abarca, Department of Internal Medicine, Escuela Medicina y Ciencias Salud, Mexico 04360, Ciudad de México, Mexico

Husna Fatima, Department of Internal Medicine, Osmania Medical College, Hyderabad 500095, Telangāna, India

Prarath Roshni, Department of Internal Medicine, JSS Medical College, Mysore 570015, Karnātaka, India

Noor Ul Huda, Department of Internal Medicine, Wah Medical College, Rawalpindi 47000, Punjab, Pakistan

Yuliya Lysak, Department of Internal Medicine, St. George's University, Grenada 00000, Saint Vincent and the Grenadines

Asad Gandapur, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States

Samantha Contreras Vazquez, Department of Medicine, Benemérita Universidad Autónoma de Puebla, Puebla 72000, Mexico

Muhammad Areeb Siddiqui, Department of Internal Medicine, Ziauddin Medical College, Karachi 75000, Sindh, Pakistan

Adetola Mowo-Wale, Department of Internal Medicine, Obafemi Awolowo College of Health Sciences, Kajola 220103, Nigeria

Co-first authors: Maneeth Mylavarapu and Ogechukwu Obi.

Author contributions: Mylavarapu M, Obi O, Abarca Y, Fatima H, Roshni P, Huda NU, Lysak Y, Gandapur A, Vazquez SC, Siddiqui MA, and Mowo-Wale A contributed to methodology; Mylavarapu M, Obi O, Abarca Y, Fatima H, Roshni P, Huda NU, and Lysak Y contributed to writing and original draft preparation; Mylavarapu M, Obi O, and Abarca Y contributed to visualization; Mylavarapu M contributed to supervision; Mylavarapu M and Obi O have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

PRISMA 2009 Checklist statement: The authors have read the PRISMA checklist of items, and the manuscript was prepared and revised according to the PRISMA checklist of items.

Corresponding author: Maneeth Mylavarapu, Senior Researcher, Department of Cardiology, Endeavor Health Cardiovascular Institute, 2100 Pfingsten Road, Glenview, IL 60026, United States. dr.maneeth.mylavarapu@gmail.com

Received: July 21, 2025
Revised: November 6, 2025
Accepted: January 19, 2026
Published online: March 26, 2026
Processing time: 246 Days and 13.9 Hours

Abstract

BACKGROUND

Obesity-related heart failure in patients is often associated with a high symptom burden. However, no treatments have been proven to specifically target obesity-related heart failure with preserved ejection fraction (HFpEF).

AIM

To evaluate the efficacy of semaglutide in patients with obesity and HFpEF.

METHODS

Per the PRISMA guidelines, studies reporting clinical outcomes of semaglutide in patients with obesity and HFpEF were included. The outcomes included percentage weight change and adjudicated heart failure events. Both random and common effects models were used for the data analysis. The random intercept logistic regression model was used to compute the proportions, and the Peto method was used to compute the odds ratios (OR). A P ≤ 0.05 was considered significant.

RESULTS

In total, three studies with 1463 patients with obesity and HFpEF were included in the study. The mean age of the patients was 68.8 ± 3.47 years. 50.7% of the patients were females. Patients who received semaglutide had statistically higher odds of achieving 10% (OR = 6.35; 95%CI: 1.54-26.21; P < 0.00001) and 15% (OR = 9.44; 95%CI: 2.91-30.60; P < 0.0001) weight reductions compared to those who received placebo. Additionally, patients who received semaglutide had lower odds of adjudicated heart failure event (OR = 0.29; 95%CI: 0.14-0.58; P = 0.0005) when compared to patients on placebo.

CONCLUSION

Our study demonstrates that semaglutide is significantly effective in reducing weight and potentially lowering the risk of heart failure events. This suggests that semaglutide could be a promising therapeutic option for managing obesity-related HFpEF.

Keywords: Semaglutide; Heart failure with preserved ejection fraction; Obesity; Weight-loss; Glucagon-like peptide-1 receptor agonists; Meta-analysis

Core Tip: This meta-analysis demonstrates that semaglutide is effective in reducing weight and potentially lowering the risk of heart failure events in patients with obesity and heart failure with preserved ejection fraction (HFpEF). This suggests semaglutide as a promising therapeutic option for managing obesity-related HFpEF, a condition with limited current treatment options. The findings showed statistically higher odds of 10% and 15% weight reduction, as well as lower odds of adjudicated heart failure events, in patients receiving semaglutide compared to those receiving placebo. Further large-scale trials are needed to confirm these benefits and explore long-term outcomes.