Endocrinol Metab.  2023 Aug;38(4):426-435. 10.3803/EnM.2023.1737.

Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis

• Kim MK
• Han K
• Kwon HS
• Yoo SJ

• KMID: 2545275
• DOI: http://doi.org/10.3803/EnM.2023.1737

Abstract

Background
The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results.
Methods
This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis.
Results
During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure.
Conclusion
In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

Keyword

Pancreatic carcinoma; Dipeptidyl-peptidase IV inhibitors; Diabetes mellitus, type 2

Figure

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  Fig. 1. Study enrollment flow diagram. DPP-4, dipeptidyl peptidase 4; GLD, glucose-lowering drug.

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  Fig. 2. Kaplan-Meier estimates of the incidence of pancreatic cancer in patients using dipeptidyl peptidase 4 (DPP-4) inhibitors (in red) versus other glucose-lowering drugs (GLDs) (in black). (A) Pancreatic cancer defined by the corresponding International Classification of Diseases 10th Revision (ICD-10) code (C25) and reimbursement V-code for cancer (V193) from the national registration data. (B) Cases diagnosed with pancreatic cancer during hospitalization, defined by the corresponding ICD-10 code (C25) and reimbursement V-code for cancer (V193) from the national registration data.

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  Fig. 3. Subgroup analysis according to baseline characteristics. Hazard ratios and 95% confidence intervals of pancreatic cancer for dipeptidyl peptidase 4 (DPP-4) inhibitors versus other glucose-lowering drugs (GLDs). CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; SUR, sulfonylurea.

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