Effect of Immortal Time Bias Controlled Metformin for Cancer Development in Diabetic Patients

Abstract

Background: This study aimed to determine the effectiveness of metformin as first line oral hypoglycemic agent in diabetes patients in inhibiting cancer incidence, on the basis of the sample cohort supplied by the National Health Insurance Service, and to ascertain the effects of time-related bias on the results.Methods: A t-test was performed to compare the time taken for cancer development between the compliant and non-compliant metformin users and the non-metformin users. Survival analyses for cancer patients, regarding the period time until cancer incidence, were performed according to metformin use through three models: model 1 adjusted for age and sex; model 2 further adjusted for body mass index, cholesterol, and smoking status;and model 3 further adjusted for hypertension.Results: The odds ratio for cancer development was 1.11 times higher for the non-metformin users (6,997) than for the metformin compliant users (16,132), which was significant at the 0.1 significance level. The age, sex, body mass index, cholesterol, smoking status, and hypertension-adjusted hazard ratio was 0.86.Conclusions: This study has confirmed that metformin is effective in delaying cancer development for patients at risk of cancer rather than in inhibiting cancer incidence itself, by strict application of metformin exposure, with which immortal time biases are controlled. It is therefore necessary to manage compliance with an agent, as well as to prescribe metformin for patients at high risk of cancer, giving consideration to the risk factors for cancer development (old age, being male) instead of focusing on metformin prescription, with the objective of inhibiting cancer development.