Association Between DPP-4 Inhibitors and Events of Colorectal and Liver Cancers in Patients With Diabetes Receiving Second-Line Agents: A Nested Case-Control Study

Chu-Lin Chou; Shu-Hui Juan; Ching-Hao Li; Hsi-Hsien Chen; Chih-Chin Kao; Li-Ying Chen; Li-Nien Chien; Te-Chao Fang

doi:10.3389/fonc.2022.840142

Association Between DPP-4 Inhibitors and Events of Colorectal and Liver Cancers in Patients With Diabetes Receiving Second-Line Agents: A Nested Case-Control Study

Front Oncol. 2022 May 6:12:840142. doi: 10.3389/fonc.2022.840142. eCollection 2022.

Authors

Chu-Lin Chou^{1

2

3}, Shu-Hui Juan⁴, Ching-Hao Li^{4

5}, Hsi-Hsien Chen^{2

3

6}, Chih-Chin Kao^{2

3

6}, Li-Ying Chen⁷, Li-Nien Chien⁸, Te-Chao Fang^{2

3

6}

Affiliations

¹ Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
² Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Taipei Medical University Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.
⁴ Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁶ Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
⁷ Health Data Analytics and Statistics Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan.
⁸ School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan.

Abstract

Objective: Plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. Until now, whether DPP4is therapy affects the progression of liver cancer and colorectal cancer in patients with T2DM has not been well investigated. We investigated the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes.

Materials and methods: We identified 268,520 patients with diabetes receiving DPP4is as second-line agents between March 1, 2009, and December 31, 2013, from Taiwan's National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry of Taiwan. The amount of DPP4is were divided into three groups (low, medium, and high) based on the interquartile range of the cDDD of the DPP4is.

Results: The data showed that the low cDDD of DPP-4is was associated with a reducing risk of colorectal cancer [adjusted odds ratio (OR), 0.49; 95% CI, 0.32-0.75; P=0.001]. However, the high cDDD of DPP-4is was associated with an increasing risk of colorectal cancer (adjusted OR, 1.86; 95% CI, 1.32-2.61; P<0.001). No association between DPP4is use and liver cancer risk was observed.

Conclusions: This nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. Therefore, the effects of long-term DPP4is use on colorectal cancer risk warrant further study.

Keywords: DPP-4 inhibitors; colorectal cancer; liver cancer; second-line agents; type 2 diabetes mellitus.