Semaglutide and tirzepatide use in patients with HFrEF was associated with significantly lower 1-year all-cause mortality compared to matched controls (HR 0.45; 95% CI 0.35-0.57 for semaglutide).
Cohort (n=5,122)
Yes
Do newer GLP-1 receptor agonists (semaglutide and tirzepatide) reduce mortality and hospitalizations in patients with HFrEF?
In a real-world cohort of patients with HFrEF, treatment with semaglutide or tirzepatide was associated with significantly lower 1-year all-cause mortality and hospitalizations compared to matched controls.
Hazard Ratio: 0.45 (95% CI 0.35–0.57)
Absolute Event Rate: 4.2% vs 9.1%
p-value: p=<0.001
Abstract Background Newer glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve outcomes in obese patients with heart failure (HF) and preserved ejection fraction with or without diabetes. However, their role in HF with reduced ejection fraction (HFrEF) remains unclear, as data from older-generation GLP-1RA trials and post hoc analyses from newer-generation GLP-1RA trials are conflicting. Purpose To assess the effect of the newer GLP-1RAs semaglutide and tirzepatide on mortality and hospitalization in patients with HFrEF. Methods We Conducted a retrospective cohort analysis using a real-world research network collaboration, incorporating data from 105 healthcare organizations. Patients with HFrEF treated with semaglutide (n=2,225) or tirzepatide (n=336) between Jul 1, 2022, and Dec 31, 2023, were compared to 1:1 propensity-score matched controls who never received GLP-1RAs (Table 1). We evaluated the following outcomes at 1 week after the inception date: (1) all-cause mortality, (2) death or HF hospitalization (HFH), and (3) death or all-cause hospitalization (ACH). Kaplan-Meier survival curves and Cox proportional hazards models were utilized to evaluate the association of GLP-1RAs with outcomes. Results In the semaglutide group, 1-year mortality was 4.2% vs. 9.1% in controls (HR: 0.45; 95% CI: 0.35-0.57; p0.001), while in the tirzepatide group, it was 3.6% vs. 8.8% (HR: 0.40; 95% CI: 0.20-0.80; p=0.007). Death or HFH rates at 1 year were significantly lower in both semaglutide and tirzepatide groups vs. controls (semaglutide: 12.5% vs. 19.1% HR: 0.62; 95% CI: 0.53-0.72; p=0.042, and tirzepatide: 11.0% vs. 18.5% HR: 0.55; 95% CI: 0.37-0.83; p=0.004). The death or ACH rates were also significantly lower with GLP-1RAs (semaglutide: 25.4% vs. 34.9% HR: 0.66; 95% CI: 0.59-0.74; p0.001, and tirzepatide: 22.9% vs. 32.1% HR: 0.65; 95% CI: 0.48-0.87; p=0.004) (Table 2). Conclusion Both semaglutide and tirzepatide were associated with lower mortality and hospitalization composite outcomes in patients with HFrEF. Semaglutide demonstrated stronger statistical significance across all endpoints. Clinically, these findings suggest that GLP-1 RAs could be an adjunctive therapy in managing HFrEF, particularly for patients with comorbid metabolic disorders. Further randomized controlled trials are necessary to validate these findings and elucidate the mechanisms underlying their cardioprotective effects.Table 1 Table 2
Rahmani et al. (2025) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=5,122). Semaglutide and tirzepatide vs. Propensity-score matched controls who never received GLP-1RAs was evaluated on 1-year all-cause mortality (HR 0.45, 95% CI 0.35-0.57, p=<0.001). Semaglutide and tirzepatide use in patients with HFrEF was associated with significantly lower 1-year all-cause mortality compared to matched controls (HR 0.45; 95% CI 0.35-0.57 for semaglutide).