GLP‐1 Receptor Agonists for the Prevention of New‐Onset Heart Failure: A Systematic Review and Meta‐Analysis of Placebo‐Controlled Randomized Clinical Trials

ABSTRACT Introduction Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) improve outcomes in heart failure (HF) with preserved ejection fraction. Whether GLP‐1 RA prevent new‐onset HF in Type 2 diabetes or obesity requires further investigation. Methods We performed an updated meta‐analysis of randomized placebo‐controlled trials (RCT) of treatment with GLP‐1 RA in participants without HF. The hazard ratio (HR) and 95% confidence intervals (95% CI) were extracted from the group without HF in each study. The primary outcome was time to first HF event (HF hospitalization or urgent visit for HF). The correlation between the effect of GLP‐1 RA on HF events and the effects on HbA1c, weight and major atherosclerotic cardiovascular events (MACE) was also investigated. We also evaluated the heterogeneity of effect according to study characteristics. Results A total of 52,752 participants without HF from six RCTs were included. Treatment with GLP‐1 RA (vs. placebo) decreased the risk of new‐onset HF (HR = 0.77 [95% CI 0.65–0.93], p < 0.001) and the composite of HF events or cardiovascular death (HR = 0.82 [95% CI 0.76–0.89], p < 0.001). The effect of GLP‐1 RA on HF events was independent of its effects on HbA1c or weight, but was correlated with its protective effects on MACE. The effects on HF prevention were more pronounced in studies restricted to patients with atherosclerotic cardiovascular disease and in trials with higher incidence rate of HF events. Conclusion Treatment with GLP‐1 RA decreases the risk of new‐onset HF in patients with Type 2 diabetes or obesity.