Oral Insulin Secretagogues, Insulin, and Cancer Risk in Type 2 Diabetes Mellitus

Background: Hyperinsulinemia might be the mechanism leading to an increased cancer risk in patients with type 2 diabetes. The objective was to evaluate the association between oral insulin secretagogues, insulins, and cancer incidence. Methods: A total of 108,920 patients with newly diagnosed type 2 diabetes were identified from the Taiwan National Health Insurance claims database during the period from 1 January 2000 to 31 December 2000. As of 31 December 2007, patients with incident cancer were included as cases, and up to four age- and sex-matched controls were selected by risk-set sampling. Logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between antidiabetic medication and cancer incidence. Results: A total of 8,194 incident cancer cases and 32,776 diabetic controls were included. A significantly increased risk for overall cancer incidence was found for any use of insulin (OR, 1.97; 95% CI, 1.85-2.09) and glinides (OR, 1.16; 95% CI, 1.06-1.28). Significantly increased risks were found for first-and second-generation sulfonylureas (OR, 1.08; 95% CI, 1.01-1.15), but not for third-generation drug, glimepiride (OR, 1.00; 95% CI, 0.93-1.08). Use of insulin and glinides was associated with higher risks for liver, colorectal, lung, stomach, and pancreas cancer, whereas sulfonylurea was mainly associated with an increased risk of liver cancer. Conclusions: The results showed that sulfonylureas and glinides increased the risk for overall cancer, but to a lesser extent than insulin. Therapies that are associated with cancer risks certainly require further investigation. (J Clin Endocrinol Metab 97: E1170-E1175, 2012)