Breast Cancer Incidence in Diabetes Mellitus Patients on Insulin Glargine Compared with Human Neutral Protamine Hagedorn Insulin Treatment

Introduction: Observational studies evaluating the association between long-acting insulins and breast cancer incidence is limited. We conducted a systematic review to compare the incidence of breast cancer between diabetes mellitus (DM) patients on long-acting insulin treatment. Methodology: We systematically searched the literatures from MEDLINE, Science Direct and PROQUEST from 2008 to 2018 to identify all observational studies evaluating the relationship between use of insulin glargine and human Neutral Protamine Hagedorn (NPH) insulin to breast cancer incidence among patients with type-1 and/or type-2 diabetes mellitus (DM) aged ≥ 18 years old. The methodological aspects such as residual confounding and duration of follow-up were assessed. Results: A total of four cohort studies met our inclusion criteria. Follow-up duration ranged from 0.9 to 3.3 years. Two studies showed the use of insulin glargine was associated with an increased risk of breast cancer in comparison with human NPH insulin and two other studies found no evidence of breast cancer. All of these studies had a short follow-up duration and were not able to examine residual confounding. Conclusion: We found limited support for association of glargine use with increased breast cancer risk compared to human NPH insulin due to the methodological issues. Further studies with better methodological aspects are needed to explain the difference of breast cancer incidence between those treatments.