A systematic review and network meta-analysis published in the Diabetes/Metabolism Research and Reviews assessed the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and intestinal cancers in patients with type 2 diabetes mellitus (T2DM). Databases including PubMed, Embase, Web of Science, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched through 13 June 2024. Seventeen randomized clinical trials comprising 36,415 participants were included. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated.

GLP-1 RA use was associated with a reduced risk of colon cancer (RR 0.34; 95% CI 0.17–0.68; I²=0.0%). The analysis showed neutral associations for colorectal carcinoma (RR 1.13; 95% CI 0.92–1.39; I²=0.0%), rectal cancer (RR 3.64; 95% CI 0.76–17.40; I²=0.0%), and intestinal cancer (RR 0.76; 95% CI 0.31–1.84; I²=23.3%). Network meta-analysis and subgroup analyses suggested a potential association between albiglutide and subcutaneous semaglutide and lower colon cancer incidence, particularly with longer treatment duration and lower baseline HbA1c, irrespective of baseline BMI, age, or comparator type.

Limitations included exclusion of newer agents due to insufficient data, inability to perform certain subgroup analyses, limited rectal and intestinal cancer data, and potential limited applicability to patients with cardiovascular risk or renal dysfunction.

Overall, GLP-1 RAs were associated with reduced colon cancer risk without increasing intestinal tumour risk in RCT populations. Larger, multicenter RCTs with longer follow-up are needed to further evaluate these associations.