Effects of Long-acting Insulin Analogues on Breast and Colon Cancer Promotion

Abstract

Insulin glargine, a long-acting insulin analogue, has been implicated in increased cancer risk by epidemiological studies and has been reported to increase mitogenicity in in vitro studies. However, studies in preclinical models confirming the tumor promoting effect of glargine are lacking. Methylnitrosourea and azoxymethane treated female Sprague-Dawley rats were randomly assigned to receive saline, neutral protamine Hagedorn (NPH, unmodified insulin), glargine, or detemir (long-acting insulin analogues) for 6 weeks (30/group). Rats treated with NPH had significantly higher mammary tumour multiplicity and a tendency to increased tumour incidence. Mammary tumour burden tended to increase in all insulin-treated rats compared to control. There was no effect of insulin on aberrant crypt foci, a precursor of colon cancer, compared to control. These data suggest that glargine does not promote breast or colon cancer to a greater extent than unmodified insulin. This is important information in the management of patients with diabetes.