Abstract
BACKGROUND: The association between dipeptidyl peptidase-4 inhibitors (DPP-4i) exposure and the risk of colorectal cancer (CRC) in patients with type 2 diabetes mellitus (T2DM) is unclear. OBJECTIVES: This meta-analysis aims to investigate the relationship between DPP-4i exposure and the incidence of CRC in patients with T2DM. DESIGN: A systematic review and meta-analysis. METHODS: A comprehensive search of electronic databases, including PubMed, Web of Science, EMBASE, and ScienceDirect, was conducted up to March 2024. The studies including randomized clinical trials (RCTs), cohort studies, and case-control studies were retrieved. The odds ratio (OR) was calculated using Stata 12.0 statistical software. The primary outcome assessed was the incidence of CRC. RESULTS: This meta-analysis incorporated six retrospective cohort studies and two case-control studies. The findings indicate that the incidence of CRC in the DPP-4i exposure group was significantly higher than that in the control group (OR = 1.11, 95% CI: 1.02-1.21, p = 0.013). Subgroup analysis revealed that both male (OR = 2.07, p < 0.001) and female participants (OR = 1.49, p = 0.05) in the DPP-4i exposure group exhibited a significantly higher incidence of CRC compared to the control group. Among participants younger than 65 years, the incidence of CRC was markedly elevated in the exposure group (OR = 2.81, p < 0.001). Furthermore, when the exposure duration was less than 1 year, the CRC incidence in the exposure group surpassed that of the control group (OR = 1.24, p = 0.005). When sulfonylureas (SU) were used as control drugs, the incidence of CRC was higher in the exposure group (OR = 1.10, p = 0.017). CONCLUSION: There is a potential correlation between DPP-4i exposure and increased incidence of CRC in T2DM patients. This association appears to be influenced by gender, age, duration of exposure, and the choice of control medications. Therefore, attention should be paid to colorectal diseases when DPP-4i is employed in the clinic. TRIAL REGISTRATION: The meta-analysis has been registered with the International Prospective Register of Systematic Reviews (PROSPERO). The registration number is CRD42024535292.