Work

Glucagon-Like Peptide-1 Receptor Agonists Improve Cardiovascular Outcomes in Heart Failure with Preserved Ejection Fraction, Independent of Diabetes: A Systematic Review and Meta-Analysis

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Heart failure (HF) with preserved or mildly reduced ejection fraction (HFpEF or HFmrEF) is often associated with obesity and metabolic dysfunction. Recent data suggest that incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and tirzepatide improve cardiovascular outcomes in patients with HFpEF or HFmrEF both with and without diabetes. However, whether the effects differ by diabetes status across the broader literature remains unclear. Methods: MEDLINE and Embase were searched through October 2025 to identify randomized controlled trials (RCTs), post-hoc RCT analyses, and observational studies evaluating GLP-1RAs and tirzepatide effects on cardiovascular outcomes in patients with HFpEF or HFmrEF. Meta-regression examined effect modification by type 2 diabetes (T2D) status. Exploratory network meta-analysis of RCTs was performed to evaluate comparative efficacy across therapies. Results: -values for interaction were > 0.05, indicating no evidence that T2D modified treatment effects. In pooled RCT analyses, incretin-based therapies significantly reduced HF hospitalization and events (hazard ratio [HR] 0.68 [95% confidence interval {CI} 0.52-0.88]) and composite of cardiovascular death or HF hospitalization and/or events (HR 0.76 [95% CI 0.65-0.87]). Pooled observational data demonstrated significant reduction in HF hospitalization and events (HR 0.60 [95% CI 0.58-0.62]). Exploratory network meta-analysis found no significant difference in efficacy between individual agents. Conclusions: Incretin-based therapies with GLP-1RA activity reduce HF hospitalization and events in patients with HFpEF or HFmrEF, with comparable benefits irrespective of T2D status. These findings support cardiovascular benefits of incretin-based therapies beyond glucose lowering and reinforce their role in obesity-associated HFpEF and HFmrEF.

Source: CJC Open

DOI: 10.1016/j.cjco.2026.02.008

Authors: Arveen Shokravi, Rishav Singh, Sohat Sharma, Jayant Seth, G.B. John Mancini

Institutions: University of British Columbia, University of Calgary

Language: English

Topic: Heart Failure Treatment and Management

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,590