# Effect of GLP-1 Receptor Agonists in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

## TL;DR

This study reviews the effects of GLP-1 receptor agonists on heart failure with preserved ejection fraction, finding no major impact on mortality but potential benefits in quality of life and heart failure events with newer drugs.

## Contribution

The study is the first to show that newer GLP-1 RAs may reduce heart failure events in HFpEF patients.

## Key findings

- GLP-1 RAs showed no significant effect on cardiovascular mortality or worsening heart failure events.
- Newer GLP-1 RAs like semaglutide and tirzepatide reduced heart failure events by 41%.
- Quality of life improved with GLP-1 RAs, and safety data favored the treatment group.

## Abstract

Heart failure with preserved ejection fraction (HFpEF) affects 32 million people worldwide and is responsible for tens of billions of dollars in healthcare expenditure annually, with costs primarily driven by hospitalizations. HFpEF is notoriously difficult to treat, but emerging studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be effective therapies. We performed a systematic review and meta-analysis of six randomized controlled trials with 5564 total participants investigating GLP-1 RAs in patients with HFpEF. Overall, no significant effect was noted for GLP-1 RAs on our primary outcomes of cardiovascular mortality and worsening heart failure (HF) events, although they were associated with improvement in quality of life measures. Furthermore, safety data favored the GLP-1 RA group, although tolerability did not differ compared with placebo. While the pooled analysis of all GLP-1 RAs showed neutral effects versus hard endpoints, sensitivity analyses excluding older-generation agents (exenatide) revealed a significant 41% reduction in HF events, suggesting that newer, more potent agents (semaglutide, tirzepatide) may offer disease-modifying benefits in HFpEF. Although future studies are needed, GLP-1 RAs appear to be promising for the treatment of HFpEF.