Long-Acting Insulin Analogues and Risk of Breast Cancer—Meta-analysis

Observational studies on the association between prescription of long acting insulin analogues (glargine and detemir) and the risk of breast cancer (BC) report conflicting results. We performed a meta-analysis of prospective studies on the risk of breast cancer among diabetic patients exposed to long acting insulin analogues following PRISMA guidelines. Summary relative risks (SRR) were computed using a random-effect model. Thirteen studies were identified which reported data on insulin glargine which included 438,214 subjects and 4,041 BC cases over a median follow-up of 2.8 years. In 11 studies, including 94.8 % of BC, the comparator groups included diabetic patients treated with non-glargine insulin. The SRR was 1.11 (95% CI: 0.98, 1.24), with little heterogeneity (I²=27%). Among prevalent users of insulin, based on 7 studies, the SRR of BC (1,425 cases) associated with prescription of glargine was 1.(95% CI: 0.90, 1.23), with moderate heterogeneity among studies (I²=40%). One influential study (Wu et al. 2017) accounted for most of the heterogeneity. When it was removed from the meta-analysis, the I² dropped to 0% with a SRR of 0.99 (95% CI: 0.88, 1.12). Among new users of insulin, based on 10 studies, the SRR of BC (3,847 cases) associated with prescription of glargine was 1.12 (95% CI: 0.96, 1.29), with moderate heterogeneity among studies (I²=41%). One influential study (Ruiter et al. 2012) accounted for most of the heterogeneity. When it was removed from the meta-analysis, the I² dropped to 0% with a SRR of 1.07 (95% CI: 0.96, 1.21). Only three studies reported on detemir, with a SRR for BC (1,947 cases) of 1.09 (95% CI: 0.77, 1.57). There seems to be consistent evidence showing no association between the prescription of long acting insulins and risk of BC. However, most of these studies had a short duration of follow-up. In addition, only three studies were identified reporting the risk of BC associated with use of detemir.