Incident Hepatocellular Carcinoma Risk in Patients Treated with a Sulfonylurea: A Nationwide, Nested, Case-Control Study

Abstract

Severalstudieshave shown that the use ofsulfonylureasinpatientswith type 2 diabetes mellitus (T2DM) is associated with a higherriskofhepatocellular carcinoma(HCC). In thisstudy, we investigated the effects of individualsulfonylureason HCC development using the National Health Insurance Service-National Sample Cohort in South Korea. Among 47,738 subjects aged 40 years or older who had newly diagnosed with diabetes, 241incidentHCC cases and 1205 matched controls were identified. Adjusted odds ratios (ORs) as estimates of the relativeriskof HCC were calculated using logistic regression analysis. Compared topatientsnevertreatedwith asulfonylurea, thosetreatedwith asulfonylureahad a 1.7-fold increasedriskof HCC development. Of the different types ofsulfonylureas, the exclusive use of glimepiride was associated with a significantly elevatedriskof HCC (OR = 1.89, 95% CI = 1.02-3.47) compared to those who were nevertreatedwithsulfonylureas. No significant associations were observed between exclusive gliclazide use andincidentHCC (OR = 2.04, 95% CI = 0.75-5.52). In conclusion, the association between the use ofsulfonylureasandriskof HCC was different according to the type ofsulfonylurea, inpatientswith new-onset T2DM. Further prospectivestudiesare warranted to confirm these results and translate them into clinical practice.