Insulin lispro: a new quick-acting insulin analogue

Insulin lispro (Humalog) is a biosynthetic insulin analogue in which the positions of proline and lysine are reversed in the C-terminal portion of the B chain. Human insulin readily self-associates into hexamers, which dissociate relatively slowly following subcutaneous injection. In consequence, there is a clinically important delay between the subcutaneous injection of soluble insulin and its maximal pharmacodynamic effect. The clinical development of lispro has been based on minor and elegant manipulation of the amino acid sequence to create an insulin which self associates poorly, and is therefore absorbed more rapidly into the circulation. By virtue of this characteristic, it has a more rapid onset of action than soluble insulin preparations, and a shorter duration of action. Potential clinical benefits include better matching of peak insulin action to food absorption following meals, and better glycaemic control in the immediate post-prandial period together with less risk of hypoglycaemia in the period before the next meal is due. An important practical advantage for patients is that the insulin injection does not have to be taken 30 min before meals, as recommended for soluble insulin, but can instead be given almost immediately before meals.