Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis

Context: Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events. Objective: To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. Data Sources: We searched MEDLINE, Embase, Web of Science, and CENTRAL from July 31, 2019 to February 8, 2020. Study Selection: Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks. Data Extraction: Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Data Synthesis: We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48 267 subjects treated with GLP-1RAs, 130 developed breast cancer compared with 107 of 40 755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76-1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48-2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. Conclusions: Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.