An in vitro study showed that insulin degludec had a low IGF-1 receptor binding affinity compared to human insulin ( 16). Insulin detemir was found to be more than 5-fold less potent than human insulin in binding to IGF-1 ( 12). A more recent review of large epidemiologic studies did not find evidence of an increased risk of malignancy among glargine-treated patients when compared with other insulin therapies ( 13). However, there are inherent limitations to such analyses. In human studies, meta-analyses comparing exogenous insulin to non-insulin antihyperglycemic therapies have shown associations of insulin with several cancers ( 14, 15). The predominant metabolite M1 has been shown to have a 0.4-fold binding affinity to the IGF-1 receptor compared with human insulin ( 13). However, glargine is rapidly degraded to metabolites. Insulin glargine was found to have a 6- to 8-fold increase in mitogenic potency and IGF-1 receptor affinity compared to human insulin. Insulin lispro and aspart are similar to human insulin on all of the above parameters, except insulin lispro was found to be 1.5-fold more potent in binding to the IGF-1 receptor compared to human insulin. Insulin and IGF-1 receptor binding affinities, and the metabolic and mitogenic potencies of insulin analogs relative to human insulin have been assessed. Because insulin analogs are modified human insulin, the safety and efficacy profiles of these insulins have been compared to human insulin ( 12). In vitro studies have demonstrated the mitogenic effects of insulin at high concentrations, as well as carcinogenic effects of insulin binding to the insulin like growth factor-1 (IGF-1) receptor, suggesting that hyperinsulinemia may promote tumorogenesis.