Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: a cohort study using metformin as the comparator

Abstract

Yu-Ching Chen,1 Victor C Kok,1,2 Ching-Hsuan Chien,1 Jorng-Tzong Horng,1,3 Jeffrey J P Tsai11Department of Biomedical Informatics, Asia University, Taichung, 2Department of Internal Medicine, Kuang Tien General Hospital, Taichung, 3Department of Computer Science and Information Engineering, National Central University, Jhongli, TaiwanIntroduction: Accumulating evidence suggests that metformin reduces incident cancer development. Few cohort studies have evaluated the risk of subsequent cancer development in diabetic cohorts receiving antidiabetic monotherapy. We conducted a population-based study in patients with new-onset type 2 diabetes treated with antidiabetic monotherapy.Methods: We identified a cohort of patients with type 2 diabetics aged ≥30 years receiving hypoglycemic monotherapy (n=7,325) from the 1998–2007 Longitudinal Health Insurance Dataset. Patients were grouped according to the antidiabetic therapy they received into metformin (n=2,223), sulfonylurea (n=3,965), glitazone (n=53), meglitinide (n=128), acarbose (n=150), and insulin (n=806) groups. Patients with preexisting cancer were excluded. All patients were followed up until cancer development, dropout, death, or until December 31, 2008. Cox’s model was used to estimate multivariable hazard ratios (HRs) adjusted for age, sex, Charlson comorbidity index, smoking-related comorbidities, alcohol use disorders, morbid obesity, pancreatitis, hypertension, monthly income, and urbanization level. The log-rank test was used to compare cumulative cancer incidence. Two-sided P-values <0.05 were required to reject the null hypothesis.Results: The overall median follow-up duration was 2.5 years (interquartile range, 3.6 years). Totally, 367 and 124 cancers developed in the sulfonylurea and metformin groups, respectively, representing an adjusted HR of 1.36 (95% confidence interval [CI], 1.11–1.67; P<0.005). No significant differences were observed between other groups. Increased adjusted HRs were observed for colorectal cancer (adjusted HR, 1.94; 95% CI, 1.15–3.27; P<0.05) and lung cancer (adjusted HR, 1.76; 95% CI, 1.00–3.07; P<0.05).Conclusion: Metformin monotherapy may be associated with a reduction in the risk for cancer development compared with sulfonylurea monotherapy. Moreover, the use of an average defined daily dose of >0.25 of metformin when compared to lower dose will contribute to a reduction of 80% risk.Keywords: type 2 diabetes, antidiabetic drug, monotherapy, metformin, sulfonylureas, cancer risk, NHIRD