Association between Cancer and Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review of Retrospective Cohort Studies

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in the management of type 2 diabetes mellitus (T2DM) owing to their established glycemic, cardiovascular, and weight-reducing benefits.However, their potential cancer risk and limited long-term data are ongoing concerns.This systematic review aimed to synthesize the most recent evidence from retrospective cohort studies that investigated the relationship between the use of GLP-1 RA and cancer risk in patients with T2DM.Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science from database inception to April 2025.Retrospective cohort studies that evaluated the risk of incident malignancy in adult patients with T2DM who were exposed to GLP-1 RAs were considered eligible.Data on the study characteristics, patient demographics, cancer types, follow-up duration, incidence rates, and hazard ratios (HRs) were extracted.The study adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.Results: Nine studies met the inclusion criteria, which encompassed various malignancies, such as pancreatic, thyroid, colorectal, breast, and skin cancer.The majority of studies did not report a significant increase in cancer risk associated with the use of GLP-1 RAs.Notably, a study reported a significant association with thyroid cancer following 1-3 years of use (HR 1.78, 95% confidence interval [CI] 1.04-3.05),whereas a study observed a reduced risk of pancreatic cancer (HR 0.524, 95% CI 0.483-0.568).No consistent associations were identified in other types of cancer. Conclusion:This review did not find consistent evidence linking the use of GLP-1 RA to an increased cancer risk in patients with T2DM.Current observational data support the continued use of GLP-1 RAs as a safe and effective therapeutic option.However, further long-term investigations are necessary to confirm these findings by utilizing homogeneous comparator therapy with an extended follow-up period.