Association between GLP-1 receptor agonists as a class and colorectal cancer risk: a meta-analysis of retrospective cohort studies

Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are extensively used in the management of type 2 diabetes mellitus (T2DM) and obesity. While these medications offer glycemic control and cardiovascular benefits, the risks have increased because of their potential impact on cancer risk, particularly colorectal cancer (CRC). This meta-analysis aimed to evaluate the association between GLP-1 RAs and CRC risk in patients receiving GLP-1 RAs. Methods This study was conducted the PRISMA guidelines. Electronic databases (PubMed, Embase, Cochrane Library Web of Science, and ClinicalTrials.gov) were searched from inception to December 2024. The inclusion criteria encompassed Studies analyzing the effects of GLP-1 RA on CRC risk in patients with T2DM. The Newcastle-Ottawa Scale was used for the quality assessment of the included cohort studies. Random-effects models were employed for the pooled analysis, and heterogeneity was evaluated using the I2 statistic. Results Seven retrospective cohort studies involving 5,066,681 patients were included. The pooled analysis revealed a significantly increased risk of CRC among patients receiving GLP-1 RAs (RR, 2.31; 95% CI, 1.82–2.93; I2 = 36%; p < 0.0001). However, the incidence of CRC was not significantly associated with GLP-1 RA use compared with other drugs (OR, 1.73; 95% CI: 0.21–14.18, p = 0.61; I2 = 100%). Quality assessment indicated a low-to-moderate risk of bias across the included studies. Conclusion Overall, this study suggests a significantly increased risk of colorectal cancer associated with GLP-1 RA use in patients receiving GLP-1 RAs. However, the incidence of CRC is not considerably high. These findings highlight the need for further long-term, large-scale clinical trials to elucidate the relationship between GLP-1 RAs and cancer risk. Clinicians should consider these results when prescribing GLP-1 RAs, particularly in patients with CRC risk factors. Graphical Abstract