Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort

There is growing evidence that patients with type 2 diabetes mellitus have increased cancer risk. We examined the association between diabetes, cancer, and cancer-related mortality and hypothesized that insulin sensitizers lower cancer-related mortality. Participants in the Diabetes Cardiovascular Risk and Evaluation: Targets and Essential Data for Commitment of Treatment study, a nationwide cross-sectional and prospective epidemiological study, were recruited from German primary care practices. In the cross-sectional study, subjects with type 2 diabetes mellitus had a higher prevalence of malignancies (66/1308, 5.1%) compared to nondiabetic subjects (185/6211, 3.0%) (odds ratio, 1.64; 95% confidence interval, 1.12-2.41) before and after adjustment for age, sex, hemoglobin A_1c, smoking status, and body mass index. Patients on metformin had a lower prevalence of malignancies, comparable with that among nondiabetic patients, whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders; inclusion of metformin in these regimens decreased the prevalence of malignancies. In the prospective analyses, diabetic patients in general and diabetic patients treated with insulin (either as monotherapy or in combination with other treatments) had a 2- and 4-fold, respectively, higher mortality rate than nondiabetic patients, even after adjustment for potential confounders (incidence of cancer deaths in patients with type 2 diabetes mellitus [2.6%] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [1.2%]). Our results suggest that diabetes and medications for diabetes, with the exception of the insulin sensitizer metformin, increase cancer risk and mortality.