Insulin and other antidiabetic drugs and hepatocellular carcinoma risk : a nested case-control study based on Italian healthcare utilization databases

Purpose: Insulin and other antidiabetic drugs may modulate hepatocellular carcinoma (HCC) risk in diabetics. Methods: We have analyzed the role of various antidiabetic drugs on HCC in a nested case-control study using the healthcare utilization databases of the Lombardy Region in Italy. This included 190 diabetic subjects with a hospital discharge reporting a diagnosis of malignant HCC and 3772 diabetic control subjects matched to each case on sex, age, date at cohort entry, and duration of follow-up. Results: Increased risks of HCC were found for use of insulin (odds ratio [OR]=3.73, 95% confidence interval [CI] 2.52-5.51), sulfonylureas (OR=1.39, 95%CI 0.98-1.99), and repaglinide (OR=2.12, 95%CI 1.38-3.26), while a reduced risk was found for use of metformin (OR=0.57, 95%CI 0.41-0.79). The risk of HCC increased with increasing duration of insulin use (OR=2.52 for <1year, 5.41 for 1-2 years, and 6.01 for 652years; p for trend