Association Between the Use of DPP4 Inhibitors and Metformin and the Risk of Cancer in Patients with Type 2 Diabetes: A Multicenter Retrospective Cohort Study Using the OMOP CDM Database

Background/Objectives. Type 2 diabetes mellitus (T2DM) has been linked to an increased risk of several cancers. However, the influence of metformin and dipeptidyl peptidase-4 inhibitors (DPP4is) on the risk of cancers remains unclear. We investigated the association between using DPP4is and/or metformin and cancer risk compared with other glucose-lowering drugs (GLDs). Methods. This retrospective multicenter cohort study was performed using 11 hospital databases standardized to the OMOP Common Data Model (CDM) within the Observational Health Data Sciences and Informatics (OHDSI) network. T2DM patients using only DPP4is and/or metformin (DPP4is/Met group) were compared with those using other GLDs (other GLD group). From 413,344 eligible patients, propensity score (PS) 1:1 matching yielded 6674 patients in each group. Cox proportional hazards models were used to analyze cancer risk, and a random-effects meta-analysis was performed to calculate hazard ratios (HRs). Results. The DPP4is/Met group exhibited a significantly lower risk of incident cancer than the other GLD group (HR, 0.54; 95% CI, 0.41–0.69). This association was consistent across all hospitals. Regarding cancer-specific distributions, the DPP4is/Met group showed lower proportions of breast and prostate cancers, whereas the other GLD group showed higher proportions of lower gastrointestinal cancers. Conclusions. In this large multicenter study, using DPP4is and metformin showed a substantial association with a lower risk of cancer in T2DM patients relative to other GLDs. These findings suggest a potential protective effect of metformin and support the neutral-to-beneficial effect on cancer of DPP4is.