Impact of GLP-1 receptor agonists on cardiovascular outcomes in heart failure with preserved ejection fraction (HFpEF): systematic review and meta-analysis.
Antony Gonzales-Uribe, Renato Ruiz-Cortez, Nicole Collantes-Silva et al.
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In 30 seconds
This systematic review and meta-analysis assessed GLP-1 receptor agonists versus placebo or other glucose-lowering agents for mortality and heart-failure hospitalization in people with HFpEF. Six studies—five randomised trials and one cohort—included 4043 patients; five evaluated semaglutide and one tirzepatide. Across studies, GLP-1 receptor agonists were associated with a lower risk of the composite of all-cause mortality or HF hospitalization (HR 0.73; 95% CI: 0.60-0.90; I² = 0%). The analysis found no significant effect on all-cause mortality alone, while the reduction in HF hospitalization alone was less certain.
Key findings
- The composite of all-cause mortality and HF hospitalization was lower with GLP-1 receptor agonists (HR 0.73; 95% CI: 0.60-0.90; I² = 0%).
- HF hospitalizations alone were lower (HR 0.57; 95% CI: 0.32-1.00), while all-cause mortality was not significantly affected (HR 0.81; 95% CI: 0.58-1.14).
- Subgroup analyses indicated greater benefits among patients with atrial fibrillation.
Why it matters
HFpEF has limited pharmacologic treatment options, and this synthesis suggests GLP-1 receptor agonists may reduce a clinically important combined outcome. The distinction between the composite result and the nonsignificant mortality finding matters when interpreting potential benefit: the evidence supports an association with fewer combined events, not a demonstrated survival benefit.
What to keep in mind
The evidence combines five randomised trials with one cohort, and the abstract does not provide detailed subgroup estimates or certainty ratings.