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New Insulin Analogues and Routes of Delivery

Pharmacodynamic and Clinical Considerations

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Abstract

Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles and provide better postprandial glucose control and less hypoglycaemia (primarily nocturnal and severe hypoglycaemia in type 1 diabetes mellitus) than regular insulin. Insulin glulisine is a new rapid-acting analogue and has characteristics nearly identical to those of its predecessors. Insulin glargine was the first basal analogue approved for clinical use and has shown better fasting glucose control and less risk of hypoglycaemia than conventional human neutral protamine Hagedorn (NPH) insulin. More recent studies have indicated that insulin glargine may not be truly ‘peakless’ at higher doses and that the adjustment of dose timing and frequency may have favourable effects on the risk of hypoglycaemia and the duration of the effect. Insulin detemir is a new basal insulin analogue with superiority to NPH insulin similar to that demonstrated by insulin glargine, though its duration of action appears to be shorter. The intraindividual variability in the response to a given dose is lower for insulin detemir than for both NPH insulin and insulin glargine. The clinical significance of this finding is not clear, though it may contribute to the lower rate of hypoglycaemia seen with insulin detemir. A number of ‘alternative routes’ of insulin administration have been studied, the most promising of which has been the pulmonary route. The time-action profile of inhaled insulins is generally characterized by a rapid onset of action similar to those of rapid-acting analogues and a slightly protracted duration of action similar to that of regular insulin. Inhaled insulin is similar to regular insulin with respect to efficacy and safety, though small reversible changes in pulmonary function have been noted. For technical and practical reasons, other alternative routes have generally not met with clinical success.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The author was employed by Eli Lilly and Company from 1995 to 2001, during which time he was involved in research and development activity related to insulin lispro. Since leaving Eli Lilly, he has participated as the principal investigator or as a site principal investigator in four Eli Lilly-sponsored clinical trials. He has been a paid consultant to Eli Lilly and Novo Nordisk on an ad hoc basis.

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    Paris Roach

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Roach, P. New Insulin Analogues and Routes of Delivery. Clin Pharmacokinet 47, 595–610 (2008). https://doi.org/10.2165/00003088-200847090-00003

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