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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.
Metabolism · 2026
Last updated 2026-05-28A review of 18 studies involving 97,800 participants found that GLP-1 drugs and tirzepatide reduced the risk of major heart and kidney problems by 12% compared to a placebo. The drugs also lowered the risk of death from any cause and from heart-related causes by 12%. While the overall effect on heart failure hospitalizations was not significant, a possible benefit was seen in obese patients.
AI summary of the abstract below.
| Journal | Metabolism, 2026 |
|---|---|
| Citations | 1 |
| Molecules | tirzepatide |
| Conditions studied | Obesity, Cardiovascular Risk Reduction, Chronic Kidney Disease, Heart Failure |
Abstract
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.
Verbatim abstract via PubMed 41207615 ↗
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