Editorial
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2024; 15(5): 818-822
Published online May 15, 2024. doi: 10.4239/wjd.v15.i5.818
Cardioprotective effects of glucagon-like peptide 1 receptor agonists in heart failure: Myth or truth?
Lorenzo Nesti, Domenico Trico
Lorenzo Nesti, Domenico Trico, Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy
Lorenzo Nesti, Domenico Trico, Laboratory of Metabolism, Nutrition, and Atherosclerosis, University of Pisa, Pisa 56126, Italy
Author contributions: Nesti L drafted the manuscript; Trico D critically revised the manuscript; All authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: Lorenzo Nesti declares no competing interests. Domenico Trico has served as an advisor for Amarin and has received fees for speaking from AstraZeneca, Eli Lilly and Novo Nordisk.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: Https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Domenico Trico, MD, PhD, Assistant Professor, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, Pisa 56126, Italy. domenico.trico@unipi.it
Received: December 5, 2023
Peer-review started: December 5, 2023
First decision: February 2, 2024
Revised: February 15, 2024
Accepted: March 18, 2024
Article in press: March 18, 2024
Published online: May 15, 2024
Processing time: 156 Days and 20.2 Hours
Abstract

Therapy with glucagon-like peptide 1 (GLP1) receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes. However, while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect, controversies remain on its impact on heart failure. GLP1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction (as demonstrated by the recent STEP-HFpEF Trial). Still, GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction (the LIVE trial). GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects (improved weight management, glycemic control, blood pressure, systemic and tissue inflammation), while direct effects on the heart have been questioned. Nonetheless, weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular functions. Tirzepatide is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide, representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular benefits. Whether this class of therapies is going to change the history of heart failure is an ongoing debate.

Keywords: Atherosclerosis; Cardiovascular system; Glucagon-like peptide-1; Heart failure; Tirzepatide; Type 2 diabetes; Ventricular function; Left

Core Tip: A growing body of evidence supports the potential cardioprotective properties of glucagon-like peptide 1 receptor agonists (GLP1-RAs) beyond glycemic control, especially in the context of cardiovascular disease. Although the effects of these drugs are consistent in reducing atherosclerosis-related diseases, there is an ongoing debate about the validity of the claim that GLP1-RAs have cardioprotective benefits in heart failure (HF)–a topic that sparks both enthusiasm and skepticism in the scientific and medical communities. Herein we provide a narrative review of the available evidence on the cardioprotective actions of GLP1-RAs in patients with HF, summarizing clinical findings and proposed mechanisms.