GLP-1RAs and tirzepatide may reduce heart failure risk in obese but not in non-obese patients with cardiovascular or renal disease: A systematic review and meta-analysis.

🥈 Top 2% JournalNov 9, 2025Metabolism: clinical and experimental

Heart Failure Risk Reduction with GLP-1RAs and Tirzepatide in Obese Patients

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Abstract

A total of 18 randomized controlled trials involving 97,800 patients demonstrated that GLP-1 receptor agonists significantly reduced the risk of cardiovascular and renal complications.

GLP-1 receptor agonists decreased the risk of the primary composite outcome by 12% (RR 0.88, 95% CI 0.84-0.91, P < 0.001).
There was a 12% reduction in the risk of death from any cause (RR 0.88, 95% CI 0.84-0.92, P < 0.001).
The risk of death from cardiovascular causes was also reduced by 12% (RR 0.88, 95% CI 0.83-0.93, P < 0.001).
No statistically significant overall effect on hospitalization for heart failure was found (RR 0.92, 95% CI 0.78-1.08), but a potential benefit was noted in obese patients (P for interaction = 0.02).
GLP-1 receptor agonists had a lower incidence of serious adverse events (RR 0.93, 95% CI 0.89-0.99, P = 0.01) and cardiac adverse events (RR 0.90, 95% CI 0.85-0.96, P < 0.01) compared to placebo.

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BACKGROUND: Cardiovascular disease (CVD) and chronic kidney disease (CKD) frequently coexist, with obesity and type 2 diabetes (T2D) being major contributors to adverse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and tirzepatide have shown cardiorenal benefits beyond glycemic control, but their efficacy across metabolic phenotypes remains unclear.

METHODS: This review was prospectively registered in PROSPERO (CRD420251088042). PubMed, Embase, Web of Science, and Cochrane Library were searched (January 2015-July 2025) for RCTs comparing GLP-1RAs or tirzepatide with placebo in patients with cardiovascular or renal disease. Subgroup analyses were performed according to T2D and obesity status.

RESULTS: A total of 18 RCTs (n = 97,800) involving eight GLP-1RAs and tirzepatide were included, primarily enrolling patients with established cardiovascular or renal disease. GLP-1RAs significantly reduced the risk of the primary composite outcome (RR 0.88, 95 % CI 0.84-0.91, P < 0.001). GLP-1RAs and tirzepatide also significantly reduced the risk of death from any cause (RR 0.88, 95 % CI 0.84-0.92, P < 0.001), and death from cardiovascular causes (RR 0.88, 95 % CI 0.83-0.93, P < 0.001). Although the overall effect of GLP-1RAs on hospitalization for heart failure was not statistically significant (RR 0.92, 95 % CI 0.78-1.08), a potential benefit was observed in obese patients (P for interaction = 0.02), warranting further investigation. GLP-1RAs showed favorable overall safety profile, with a lower incidence of serious adverse events (RR 0.93, 95 % CI 0.89-0.99, P = 0.01) and cardiac adverse events (RR 0.90, 95 % CI 0.85-0.96, P < 0.01) compared with placebo.

CONCLUSION: In patients with cardiovascular or renal disease, GLP-1RAs and tirzepatide provide consistent cardiovascular and renal protection, with a possible benefit in reducing hospitalization for heart failure among individuals with obesity.