Letter to the Editor from Han and Xu: "Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes".

Abstract

Dipeptidyl peptidase 4 inhibitor (DPP4i) is considered the “smartest hypoglycemic drug” and was found to inhibit tumor growth. Recently, a national study from Na et al reported that patients with diabetes undergoing DPP4i treatment had a higher risk of liver cirrhosis and cancer, end-stage renal disease (ESRD), and pancreatic cancer than those without DPP4i treatment (1). This result is worthy of our examination and consideration, and we have the following concerns and present the following analysis. Previous studies have shown that DPP4i markedly inhibits liver fibrosis development by suppressing activated hepatic stellate cells and collagen synthesis (2). DPP4i can inhibit the development of hepatocellular carcinoma by blocking the Snail/DPP4/CXCL10 pathway (3). Obviously, the research of Na et al does not support this conclusion. Although it is a large sample cohort study, some key factors affecting the endpoint event are missing when adjusting for confounding factors, such as lifestyle (intake of nitrite) and disease history. For example, chronic hepatitis is the main risk factor leading to liver cirrhosis and liver cancer. Another large cohort study showed that DPP4i can reduce the risk of hepatocellular carcinoma in patients with type 2 diabetes mellitus (T2DM) complicated by chronic hepatitis C infection (4), indicating that the increased risk of liver cirrhosis and cancer in this study might be caused by other omitted factors.