This meta-analysis of 12 placebo-controlled trials (n=95,023) found GLP-1 receptor agonists reduced heart failure events by 12% (NNT 238), and by 19% (NNT 167) in patients without baseline HF. Semaglutide specifically reduced HF events by 16% overall and by 31% in those without prior HF (NNT 80). Absolute benefits are modest but clinically relevant given the widespread use of GLP-1 therapy in type 2 diabetes and obesity management.
The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomised controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified heart failure event endpoint. Random effects meta-analysis using the Mantel-Haenszel Method was performed to synthesise risk ratios (RR), ARRs, and NNTs with 95% confidence intervals (CI).
Twelve placebo-controlled RCTs involving 95 023 patients were included. GLP-1 receptor agonists reduced HF events by 12% (RR 0.88, 95% CI 0.82-0.95; ARR 0.42%, 95% CI 0.17%-0.62%; NNT 238, 95% CI 161-588), and, in those without baseline HF, by 19% (RR 0.81, 95% CI 0.72-0.90; ARR 0.60%, 95% CI 0.32%-0.89%; NNT 167, 95% CI 113-313). Semaglutide reduced the risk of HF events by 16% (RR 0.84, 95% CI 0.74-0.95; ARR 0.62%, 95% CI 0.19%-1.00%; NNT 161, 95% CI 100-526), and by 31% in those without baseline HF (RR 0.69, 95% CI 0.55-0.88; ARR 1.25%, 95% CI 0.48%-1.82%; NNT 80, 95% CI 55-208).
GLP-1 receptor agonists have limited absolute benefit for preventing HF events in patients with type 2 diabetes and/or obesity, including in those without baseline HF. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD420251074882.
