Advances in the treatment of diabetes-insulin analogues

Insulin analogues are molecules derived by modifying the structure of the human insulin molecule, resulting in altered physico-chemical, biological and pharmacodynamic properties. The pharmacokinetic characteristics of the previously available rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. All currently available analogues have been shown to have a more physiological time-action profile with either a shorter onset and shorter duration of action (insulin lispro and insulin aspart) or a more constant effect lasting at least 24 hours (insulin glargine). These advantages in the time-action profiles have been shown to improve various surrogate parameters (e.g., postprandial blood glucose concentrations) in a number of randomized controlled trials. Insulin analogues also represent a unique tool to unravel structure-function relationships in insulin biochemistry and insulin action. Data on the currently available, currently tested and currently being developed analogs are reviewed.