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

Background and aim: Several studies showed 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. The aims of this study were to investigate the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes mellitus. Methods In this nested case-control study, 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. Of these, 948 and 990 patients newly were diagnosed with liver and colorectal cancer, respectively. 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 The novel finding of this nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. A large-based longitudinal investigation is necessary to determine whether long-term DPP4is exposure increase colorectal cancer risk.