Long‐acting Insulin Analogues

Abstract

Insulin has a relatively short half-life after subcutaneous injection. From early in the development of insulin as a treatment for diabetes, an important pharmacological aim has been to develop insulin formulations with longer durations of action. This in turn has allowed different clinical patterns of insulin use, ideally coming closer to physiological insulin secretion. Key to this has been the development of forms of insulin with a longer duration of action and less of a pharmacokinetic and pharmacodynamic peak. This was initially approached in the 1940s and 1950s using some elements of the physiology of insulin secretion with the development of insulin zinc suspensions and isophane formulations of insulin. The last 20 years have seen the development of a range of genetically modified insulin analogues offering much longer duration of action with a flatter action profile. Insulin glargine and insulin detemir were the first long-acting insulin analogues, but these did not always have a 24 hour duration of action in every patient. Biosimilar formulations of U100 glargine are now available, and these are marketed at a lower cost than the original glargine insulin. Newer long-acting insulin analogues such as insulin degludec and U300 glargine appear to have a true 24 hour duration of action and reduce the risk of hypoglycaemia when used in a treat-to-target approach in patients with type 1 and type 2 diabetes.