Metformin Treatment and Cancer Risk: Cox Regression Analysis with Time-Dependent Covariates of 320,000 Individuals with Incident Diabetes Mellitus
Menée sur la période 2002-2012 en Israël auprès de 315 890 personnes diabétiques âgées de 21 à 87 ans, cette étude analyse l'association entre un traitement par la metformine et le risque de cancer
There is conflicting evidence regarding the association between metformin use and cancer risk in diabetic patients. During 2002-2012, we followed a cohort of 315,890 incident diabetic individuals aged 21-87 years insured in the largest health maintenance organization in Israel. We used a discrete form of the weighted cumulative metformin exposure to evaluate its association with cancer incidence. This was implemented in a time-dependent covariate Cox model, adjusting for treatments with other glucose lowering medications, as well as age, sex, ethnic background, socioeconomic status, smoking (for bladder and lung cancer) and parity (for breast cancer). We excluded from the analysis the metformin exposure in the year before cancer diagnosis to minimize reverse causation of cancer on changes in medication. Estimated hazard ratios (HRs) that were associated with exposure to 1 defined daily dose of metformin over the previous 2-7 years were: for all-sites cancer (excluding prostate and pancreas) HR=0.98 (95% confidence interval (CI) 0.82, 1.18); colon cancer, HR=1.05 (95%CI 0.67, 1.63); bladder cancer, HR=0.98 (95%CI 0.49, 1.97); lung cancer, HR=1.02 (95%CI 0.59, 1.78); and female breast cancer, HR=0.88 (95%CI 0.56, 1.39). Our results do not support an association of metformin treatment with the incidence of major cancers (excluding prostate and pancreas).