Glucagon-like peptide-1 receptor agonists and risk of gastrointestinal cancers: A systematic review and meta-analysis of randomized controlled trials

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used for glucose lowering and weight-loss. However, their association with gastrointestinal cancer remains uncertain. This meta-analysis assesses the risk of gastrointestinal cancer in patients treated with GLP-1 RAs.

Methods

We searched Medline/PubMed, Embase, and Scopus databases from inception to November 15, 2023, for randomized controlled trials (RCTs) with at least 24 weeks of safety follow-up. Pooled risk ratios (RRs) were calculated using fixed- and random-effect models. Risk of bias was assessed using the revised Cochrane risk-of-bias tool, and certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Results

We included 90 RCTs with 124,791 participants, with an average follow-up of 3.1 years per participant. No significant association was found between GLP-1 RAs and the risk of any gastrointestinal cancer (RR_random=0.99, 95 % CI: 0.86−1.13), or site-specific gastrointestinal cancers including biliary tract (RR=0.98, 0.54−1.78), colorectal (RR=1.13, 0.92−1.39), gallbladder (RR=1.32, 0.43−4.00), gastric (RR=0.88, 0.58−1.33), hepatic (RR=0.79, 0.51−1.21), oesophageal (RR=0.70, 0.38−1.28), pancreatic (RR=1.05, 0.77−1.43), and small intestine cancer (RR=0.78, 0.20−3.04). The corresponding absolute risk differences excluded important impacts on risk. Additional analyses, limited to placebo-controlled trials, high-dose studies, or those with a follow-up duration of ≥5 years, confirmed these findings. Risk of bias was generally low and the certainty of evidence was high for all outcomes.

Conclusions

This meta-analysis found no significant impact of GLP-1 RAs on gastrointestinal cancer risk. Long-term safety monitoring of these agents remains important.

Systematic review registration

CRD42023476762.