# 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

## TL;DR

This study found that using DPP4 inhibitors and metformin in type 2 diabetes patients is linked to a lower cancer risk compared to other diabetes drugs.

## Contribution

The study provides new evidence that DPP4 inhibitors and metformin may protect against cancer in T2DM patients.

## Key findings

- Patients using DPP4 inhibitors and/or metformin had a 46% lower cancer risk compared to those using other glucose-lowering drugs.
- The protective effect was consistent across all 11 hospitals in the study.
- The DPP4/Met group showed lower rates of breast and prostate cancers compared to other groups.

## Abstract

Type 2 diabetes mellitus (T2DM) is known to be related to an increased risk of several cancers. However, the effects of specific glucose-lowering drugs on cancer development remain uncertain. In this large multicenter cohort study using databases from 11 hospitals in Korea, we compared patients prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) and/or metformin with those treated with other glucose-lowering drugs. After carefully balancing the groups, our findings showed that the group treated with DPP4is and/or metformin had a significantly lower risk of cancer, with consistent results across all institutions. These results suggest that metformin and DPP4is may have a protective role against cancer in T2DM patients, supporting their safety and potential benefits for long-term health outcomes.

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.