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GLP-1 receptor agonists reduce new-onset heart failure risk in patients with diabetes or obesity

GLP-1 receptor agonists reduce new-onset heart failure risk in patients with diabetes or obesity
Photo by Gizem Nikomedi / Unsplash
Key Takeaway
Consider GLP-1 RA's potential HF prevention benefit in diabetes/obesity, noting effect correlates with MACE protection and varies by subgroup.

This systematic review and meta-analysis examined the effect of GLP-1 receptor agonists (GLP-1 RA) on preventing new-onset heart failure in patients without HF. It pooled data from six randomized, placebo-controlled trials involving 52,752 participants with Type 2 diabetes or obesity. The primary outcome was time to first HF event (hospitalization or urgent visit).

The analysis found GLP-1 RA treatment significantly decreased the risk of new-onset heart failure, with a hazard ratio (HR) of 0.77 (95% CI 0.65-0.93, p < 0.001). It also reduced the risk of a composite outcome of HF events or cardiovascular death (HR = 0.82, 95% CI 0.76-0.89, p < 0.001). The authors noted the effect on HF events was independent of changes in HbA1c or weight but correlated with the drugs' protective effects on major adverse cardiovascular events (MACE). Effects were more pronounced in studies restricted to patients with atherosclerotic cardiovascular disease and in trials with higher HF event incidence rates.

Key limitations include the absence of reported absolute event numbers or rates, which prevents calculation of absolute risk reduction or number needed to treat. Safety, tolerability, and discontinuation data were not reported. The duration of follow-up for the included trials was also not specified. Funding sources and author conflicts of interest were not reported. The practice relevance of these findings should be interpreted with caution, as the evidence is derived from a meta-analysis where effects varied by patient subgroup and underlying HF event risk.

Study Details

Study typeMeta analysis
Sample sizen = 52,752
EvidenceLevel 1
PublishedApr 2026
View Original 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.
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