Insulin glargine use and breast cancer risk: Associations with cumulative exposure

Background: This study was aimed to assess the risk of breast cancer associated with exposure to insulin glargine in women with type 2 diabetes and evaluate whether the pattern of risk concurs with the hypothesized trend of an increase in risk with longer duration of use, taking into account previous cumulative exposure to other types of insulin.Methods: We performed a restrospective cohort study (2002-2013) in the Clinical Practice Research Datalink among adult female patients with a first ever insulin prescription (n=12 468). Time-dependent exposure measures were used to assess associations with duration of use of: (1) other insulin types before glargine was first prescribed (i.e. among switchers); and (2) of glargine during follow-up. Analyses were performed separately for insulin-naive glargine users and patients switched to glargine. Cox proportional hazards models were used to derive p-trends, hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer associated with glargine use.Results: During 66 151 person years, 186 breast cancer cases occurred; 76 in glargine users (3.0/1000 years) and 110 in users of other insulins (2.7/1000 years). Among insulin-naive women, no association with cumulative glargine use was observed (p-trend=0.91), even after5 years (HR=1.06, 95% CI 0.48-2.33). Among switchers, a linear trend with years of prior exposure to other insulins was found (p-trend=0.02). An increased risk was observed in glargine users with extensive (>3 years) past exposure to other insulins (HR=3.17, 95% CI 1.28-7.84). A non-significant trend with cumulative glargine exposure was found among switchers (p-trend=0.24).Conclusions: Exposure to glargine was not associated with an increased breast cancer risk in insulin-naive patients. Exposure to other insulins prior to the start of glargine appears to be relevant when studying breast cancer risk associated with glargine use.