Insulin therapy and biliary tract cancer: insights from real-world data

OBJECTIVE: The association between insulin therapy and the risk of biliary tract cancer (BTC) is uncertain. We aimed to assess this risk in type 2 diabetic patients. METHODS: Using electronic medical data from the Shanghai Hospital Link database, 202,557 patients with type 2 diabetes (164,997 insulin never-users and 37,560 insulin ever-users) were identified in this study between January 1, 2013, and December 31, 2016, with follow-up until December 31, 2019. By propensity score matching, an ever-user was matched with a never-user. Cox proportional hazards regression analysis was used to estimate risk ratios (HRs) and 95% CIs for three subtypes of BTC (intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC)). RESULTS: At a mean follow-up of 5.33 years, 143 cases of BTC were observed. The crude incidence rates (per 100,000 person-years) of ECC, ICC, and GBC in ever-users:never-users were 10.22:3.63, 2.04:2.04, and 8.17:6.01, respectively. Insulin therapy was associated with an increased risk of ECC (HR, 4.10; 95% CI, 1.54–10.92; P = 0.005) compared to patients who never used insulin. No statistically significant results were observed for insulin and ICC/GBC. Consistent results were also found in the original cohort. CONCLUSIONS: The relationship between insulin therapy and BTC is type-specific. Further studies are warranted to provide evidence on the identification of ECC risk groups among type 2 diabetic patients.