Related Experiment Video

Updated: Jun 23, 2026

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction
03:42

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction

Published on: March 29, 2024

Glucagon-Like Peptide-1 Receptor Agonists Improve Cardiovascular Outcomes in Heart Failure with Preserved Ejection

Arveen Shokravi1,2, Rishav Singh2, Sohat Sharma2

  • 1Department of Medicine, Cumming School of Medicine, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada.

CJC Open
|June 22, 2026
PubMed

Insights

Incretin-based therapies, including GLP-1RAs, significantly reduce heart failure hospitalizations and events in patients with HFpEF or HFmrEF. These benefits are consistent regardless of type 2 diabetes status, supporting their use in obesity-related heart failure.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF) is linked to obesity and metabolic issues.
  • Incretin-based therapies like GLP-1RAs and tirzepatide show promise for cardiovascular outcomes in HFpEF/HFmrEF patients.
  • The impact of these therapies based on diabetes status requires further investigation.

Purpose of the Study:

  • To evaluate the efficacy of incretin-based therapies (GLP-1RAs and tirzepatide) in patients with HFpEF or HFmrEF.
  • To determine if type 2 diabetes status modifies the cardiovascular benefits of these therapies.
  • To compare the efficacy of different incretin-based agents.

Main Methods:

  • A systematic search of MEDLINE and Embase identified relevant RCTs, post-hoc analyses, and observational studies.
  • Meta-regression was used to assess the effect of type 2 diabetes on treatment outcomes.
  • Exploratory network meta-analysis compared the efficacy of different incretin-based agents.

Main Results:

  • Eleven studies were included in the analysis.
  • Meta-regression showed no significant modification of treatment effects by type 2 diabetes status (P > 0.05).
  • Incretin-based therapies significantly reduced HF hospitalization/events (HR 0.68) and cardiovascular death or HF events (HR 0.76) in RCTs, and HF hospitalization/events (HR 0.60) in observational studies. No significant differences were found between individual agents.

Conclusions:

  • Incretin-based therapies effectively reduce HF hospitalizations and events in HFpEF/HFmrEF patients.
  • The cardiovascular benefits are consistent across patients with and without type 2 diabetes.
  • These findings highlight the role of incretin-based therapies in managing obesity-associated HFpEF/HFmrEF, extending beyond glucose control.
Abstract

Keywords:
cardiovascular outcomesglucagon-like peptide-1 receptor agonistsheart failure with mildly reduced ejection fractionheart failure with preserved ejection fractionincretin therapiesmeta-analysistype 2 diabetes

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