A meta-analysis of retrospective cohort studies found glucagon-like peptide-1 receptor agonist use was associated with a significantly increased risk of colorectal cancer.

A total of 5,066,681 patients were included across seven retrospective cohort studies. Adhering to PRISMA guidelines, the authors conducted a pooled analysis of studies analyzing the effects of glucagon-like peptide-1 receptor agonist (GLP-1 RA) on colorectal cancer (CRC) risk in patients with type 2 diabetes mellitus. The quality of the included studies was rated low to moderate risk of bias using the Newcastle-Ottawa Scale.

The pooled analysis revealed a more than doubled risk of CRC in patients receiving GLP-1 RAs (relative risk [RR], 2.31; p < 0.0001). However across the seven studies, three compared the incidence rates of patience receiving GLP-1 RAs to other drugs such as DPP-4 or metformin. In this pooled analysis, incidence of CRC was not significantly associated with GLP-1 RAs compared to other drugs (OR: 1.73 [0.21–14.18], p = 0.61), leading study authors to conclude that while the risk associated with GLP-1 RAs is significantly high, the incidence of CRC is not.

Potential mechanisms included GLP-1 RA–related intestinal mucosal hyperplasia, altered gut microbiota, and changes in gastrointestinal tissue turnover. Yet large cardiovascular outcome trials, such as LEADER, have not consistently demonstrated elevated cancer risk, leaving uncertainty about causality. 

“These findings require further investigation regarding the long-term safety of GLP-1 RAs in populations receiving GLP-1 RAs,” said Ying Zhong, PhD, of the West China Hospital of Sichuan University-Ziyang Hospital, China, and colleagues “Further long-term clinical trial-based research should be conducted on a larger scale to highlight the potential relationship between GLP-1 RAs and cancer risk in various populations.”

The study authors also urged clinicians to consider these findings when prescribing GLP-1 RAs, particularly in the cases of patients with preexisting CRC risk factors. Personalized risk–benefit assessments or potentially heightened CRC surveillance in high-risk individuals could help to manage the increased risk in this patient population.

Source: BMC Gastroenterology