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The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences

Lookup NU author(s): Emeritus Professor Philip Home


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Postprandial glucose excursions can inhibit achievement of good glycaemic control, and possibly have a specific effect on the risk of vascular comorbidities. Rapid-acting analogues control these excursions better than human insulin because their pharmacokinetic/pharmacodynamic (PK/PD) profile is closer to that of meal-time endogenous insulin secretion. Review of the findings of PK/PD studies and clinical trials suggests that the three marketed rapid-acting analoguesinsulin lispro, insulin aspart and insulin glulisineare equally efficacious and safe. In comparison with human insulin when using the same basal insulin, they provide comparable glycaemic control with a reduced risk of hypoglycaemia, although the combination of rapid-acting and basal analogues reduces glycated haemoglobin (HbA1c) more than human meal-time insulin combined with neutral protamine Hagedorn (NPH) insulin. Some studies have suggested that insulin glulisine has a slightly faster onset of action compared with insulin lispro or insulin aspart, but this has not been translated into demonstrable clinical benefit. Treatment satisfaction in patients with diabetes has been higher when therapy with a rapid-acting analogue is used instead of human insulin, perhaps due to differences in advised timing of injection. The largest benefits in efficacy, hypoglycaemia incidence, treatment satisfaction and quality of life have occurred when patients receive an all-analogue meal-time plus basal regimen as compared with an all-human insulin regimen. No new safety issues have been identified with the marketed rapid-acting analogues, and their insulin-like growth factor 1receptor affinity and mitogenic activity are comparable to human insulin.

Publication metadata

Author(s): Home PD

Publication type: Review

Publication status: Published

Journal: Diabetes, Obesity and Metabolism

Year: 2012

Volume: 14

Issue: 9

Pages: 780-788

Print publication date: 09/03/2012

ISSN (print): 1462-8902

ISSN (electronic): 1463-1326



DOI: 10.1111/j.1463-1326.2012.01580.x