Safety of insulin analogues: what to evaluate, how to do it, and how to interpret the results

Endocrinología y nutrición : órgano de la Sociedad Española de Endocrinología y Nutrición
Antonio Hernández MijaresDanilo Verge

Abstract

The widespread use of insulin analogues is based not only on the pharmacokinetics of these preparations, which is much closer to the physiology of insulin secretion under normal conditions, but also on their safety and effectiveness. The publication of a possible association between the use of a long-acting insulin analogue (glargine) and breast cancer has caused uneasiness among the medical community regarding the safety of these analogues. The mechanism of increased tumor activity of insulin analogues is explained by the fact that they act through insulin receptors (IR) and insulin-like growth factor-1 (IGF-1R), stimulating cell growth and inhibiting apoptosis. There are two major mechanisms: an increase in the binding time of insulin to IR and increased activation of IGF-1R. Therefore, to evaluate the safety of an analogue, the slower dissociation rate from its insulin receptor must be excluded, as well as the increased affinity for the IGF-1 receptor. This is equivalent to an index of mitogenic/metabolic activity of less than 1. These aspects can only be evaluated through study of cell lines and animal testing, which are reductionist models that cannot always be extrapolated to humans. To date, there are no data to question...Continue Reading

References

Nov 10, 2000·International Journal of Cancer. Journal International Du Cancer·P TonioloA Zeleniuch-Jacquotte
Nov 29, 2007·Journal of the National Cancer Institute·Vasundara VenkateswaranMichael Pollak
May 10, 2008·Archives of Physiology and Biochemistry·Paolo RossettiGeremia B Bolli
Nov 26, 2008·Nature Reviews. Cancer·Michael Pollak
Jan 16, 2009·Diabetes/metabolism Research and Reviews·Doron WeinsteinHaim Werner
Jul 15, 2009·Diabetologia·U Smith, E A M Gale

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