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Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
The potential of glucagon-like peptide-1 receptor agonists in heart failure
Frederik Flindt Kreiner1, G Kees Kornelis Hovingh1,2, Bernt Johan von Scholten1
1Global Chief Medical Office, Novo Nordisk A/S, Søborg, Denmark.
Insights
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise in reducing heart failure (HF) hospitalizations. These drugs may offer cardioprotective benefits by managing diabetes, obesity, and inflammation.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Heart failure (HF) presents a significant unmet medical need with high morbidity and mortality.
- HF is closely linked with cardiometabolic diseases like diabetes, obesity, and chronic kidney disease.
- Integrated strategies addressing these intertwined conditions are highly desirable.
Purpose of the Study:
- To review the emerging evidence for the cardioprotective effects of GLP-1 RAs in HF.
- To explore the potential of GLP-1 RAs as a therapeutic strategy for HF patients.
- To identify the most relevant HF phenotypes for GLP-1 RA treatment.
Main Methods:
- Analysis of data from large cardiovascular outcomes trials (CVOTs) of GLP-1 RAs.
- Review of meta-analyses examining GLP-1 RA efficacy in HF.
- Examination of mechanistic studies investigating GLP-1 RA effects on cardiovascular health.
Main Results:
- CVOTs indicate a significant relative risk reduction in HF hospitalizations with GLP-1 RAs.
- A meta-analysis of eight GLP-1 RA CVOTs showed an 11% relative risk reduction for HF hospitalization.
- Mechanistic insights suggest indirect cardioprotective benefits through improved glycemic control, weight reduction, and reduced inflammation.
Conclusions:
- GLP-1 RAs demonstrate potential as a cardioprotective strategy in heart failure.
- HF with preserved ejection fraction in patients with obesity (with or without diabetes) appears to be the most relevant phenotype for GLP-1 RA therapy.
- Further research is warranted to fully elucidate the role of GLP-1 RAs in HF management.
Abstract:
Heart failure (HF) remains one of the cardiovascular diseases (CVDs) associated with a high unmet medical need due to high morbidity and mortality rates and lack of efficacious interventions. HF is closely related to cardiometabolic diseases such as diabetes, obesity and chronic kidney disease, and strategies that address most or all these intertwined conditions are desirable. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved for type 2 diabetes (T2D), and some are also indicated for reduction of the risk of atherosclerotic CVD in T2D and for weight management. As we summarise in this concise review, preliminary evidence suggests that the cardioprotective benefits of GLP-1 RAs may also extend to HF. The most robust clinical evidence arguably originates from the large cardiovascular outcomes trials (CVOTs) completed for most GLP-1 RAs, of which the latest showed a significant relative risk reduction (RRR) of 39% (HR) with once-weekly efpeglenatide on HF requiring hospitalisation, corroborating a meta-analysis which found a significant RRR across eight GLP-1 RA CVOTs of 11%. Further, although incompletely described, multiple studies are available to provide insights into the mechanistic underpinnings, which appear to be associated mostly with indirect cardioprotective benefits owing to the ability of GLP-1 RAs to address hyperglycaemia, and reduce body weight, and, amongst others, inflammation. In sum, current evidence positions GLP-1 RAs as a potential cardioprotective strategy in HF, with HF with preserved ejection fraction emerging as the clinically most relevant phenotype for the drug class, especially when occurring in people with obesity with and without diabetes.
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