Comparative safety of diabetes medications and risk of incident invasive breast cancer: a population-based cohort study.

Abstract

Growing evidence suggests that certain commonly used diabetes medications have the potential to differentially alter breast cancer risk. We evaluated the influence of metformin, insulin, and sulfonylureas on risk of incident invasive breast cancer. We conducted a retrospective cohort study of women ≥40 years of age enrolled in a health plan between 1996 and 2011. Ever, current (≤12 months), and duration (<1, 1-2.9, ≥3 years) of diabetes medication use were obtained from pharmacy databases and modeled as time varying. Multivariable Cox proportional hazards models adjusting for potential confounders including screening mammography and body mass index were used to estimate hazard ratios (HRs) and 95% Confidence Intervals (CIs). Among 10,050 women with diabetes, 57 % used metformin, 43 % used sulfonylureas, 32 % used insulin, and 301 were diagnosed with breast cancer over median follow-up of 6.7 years. Results suggested no significant decreased risk of breast cancer among metformin users (HR 0.86; 95% CI 0.65-1.12). We found no association between increased breast cancer risk and long-acting insulin (HR 0.95; 95% CI 0.51-1.77), but reduced risk with short-/rapid-acting insulin (HR 0.69; 95% CI 0.50-0.94), and suggestion of a dose-response with increasing duration of short-/rapid-acting insulin use (HR 0.87; 95% CI 0.76-1.00). Estimates for sulfonylurea users suggested increased risk with ever use (HR 1.18; 95% CI 0.90-1.53) and with longer durations of use (≥3 years: HR 1.23; 95% CI 0.88-1.73), but confidence intervals included 1.0. Our results provide little support for the previously hypothesized decreased risk of breast cancer with metformin use or for an increased risk with insulin use. Implications for possible residual confounding by screening mammography and comorbidity should be considered in breast cancer pharmacoepidemiology studies.