Meta-analysis of placebo-controlled GLP-1 RA RCTs (including SUSTAIN, LEADER, SELECT, FLOW) calculating absolute risk reduction (ARR) and number needed to treat (NNT) for prevention of heart failure events in T2DM and/or obesity. Quantifies clinically meaningful HF prevention across GLP-1 RA drug class including semaglutide. Provides the NNT framework that clinicians need to communicate GLP-1 RA HF prevention benefits to patients and payers—translating relative risk reductions from trials into absolute benefit estimates actionable in individual clinical decisions.
Abstract
BACKGROUND AND AIMS: Heart failure (HF) is a common sequela of diabetes and obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists may prevent HF events. This meta-analysis estimates absolute risk reduction (ARR) and number needed to treat (NNT) for GLP-1 receptor agonists to prevent one HF event in patients with type 2 diabetes and/or obesity, including in those without baseline HF.
METHODS: 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).
RESULTS: 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).
CONCLUSIONS: 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.