Association Between GLP‐1 Receptor Agonists and the Risk of Colon Cancer in Adults With Type 2 Diabetes or Obesity: A Systematic Review and Network Meta‐Analysis

ABSTRACT Background and Objective To evaluate the association between glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and intestinal cancers and to explore the risk factors for these associations. Methods PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched through 13 June 2024, to identify randomised clinical trials (RCTs) assessing the relationship between GLP‐1 RA use and colorectal, colon, rectal, and intestinal cancers. Pooled relative risks (RRs) and 95% confidence intervals (CIs) for each outcome were calculated. Results In 17 RCTs comprising 36,415 patients, GLP‐1 RAs was associated with a significantly reduced risk of colon cancer (RR, 0.34; 95% CI, 0.17–0.68; I 2 = 0.0%), and showed a neutral effect on the risk of colorectal carcinoma, rectal, and intestinal cancer, with RRs of 1.13 (95% CI, 0.92–1.39; I 2 = 0.0%), 3.64 (95% CI, 0.76–17.40; I 2 = 0.0%), and 0.76 (95% CI, 0.31–1.84; I 2 = 23.3%), respectively. In the network meta‐analysis and subgroup analysis, a potential association was observed between albiglutide and subcutaneous semaglutide and a lower incidence of colon cancer among adults treated for a longer duration and with lower baseline HbA1c levels, regardless of baseline body mass index, age, or type of control group. Conclusions GLP‐1 RAs may be associated with a lower risk of colon cancer in adults with type 2 diabetes mellitus, warranting further validation in trials among high‐risk populations. Trial Registration The study protocol was pre‐registered and published on PROSPERO (CRD: 42024548010; https://www.crd.york.ac.uk/prospero/#recordDetails )