The metabolic and mitogenic properties of basal insulin analogues

Abstract

Context: Retrospective, observational studies have reported an association between diabetes treatment with insulin and a higher incidence of cancer.

Objective: Overview the literature for in vitro and in vivo studies of the metabolic and mitogenic properties of basal insulin analogues and assess the implications for clinical use.

Methods: Relevant studies were identified through PubMed and congress abstract database searches; data on metabolic and mitogenic signalling in relation to insulin treatment of diabetes are included in this review.

Results: The balance of evidence shows that although some analogues have demonstrated mitogenic potency in some in vitro studies in cancer cell lines, these findings do not translate to the in vivo setting in animals or to the clinical setting in humans.

Conclusions: The current consensus is that there is no clinical or in vivo evidence to indicate that any commercially available insulin analogue has carcinogenic effects. Large-scale, prospective clinical and observational studies will further establish any potential link.

Figure 1.

Schematic illustration of the sequence homology between the IR and IGF-R (Siddle et al., 2001). IR = insulin receptor; IGF-R = insulin growth factor receptor. Copyright requested.

Figure 2.

Schematic diagram showing the modifications to the insulin structure for the long-acting insulin analogues, insulins glargine, detemir and degludec (Agin et al., 2007). Copyright requested.

Figure 3.

Schematic diagram showing the metabolism of insulin glargine (Sommerfeld et al., 2010).