Abstract
Insulin supplementation is essential for patients with type 1 diabetes mellitus. In patients with type 2 diabetes mellitus, it is often needed for satisfactory metabolic compensation.
Replacement of the physiological insulin secretion (by injections or inhalation) has several pitfalls difficult to overcome. Exogenous insulin is injected into an improper site (maximum concentration does not reach hepatocytes through the portal vein) and its pharmacokinetics only roughly mimics the insulin secretion by beta-cells.
It has been shown gradually that to obtain rapid onset of action of subcutaneous insulin, the formation of insulin hexamers that are the actual and major cause of reduced insulin uptake has to be prevented. The first human insulin analogue, lispro, made it possible for the diabetes therapy to get closer to the ideal, as its profile after subcutaneous administration almost mimicked the physiological insulin secretion.
It has proven effective in reducing postprandial blood glucose fluctuations. The fact that glycated hemoglobin did not decrease was the point of departure for a better understanding of the rationale of insulin replacement therapy.
The advantages and full benefit of the rapid-acting insulin analogue were only obtained when combined with two NPH insulin doses. Further progress in this regard was made by using long-acting insulin analogues in combination with rapid-acting insulin analogues to mimick almost exactly the physiological insulin secretion, thus showing that the rapid-acting insulin analogues are a real contribution to the therapy of diabetes.
The most recently marketed rapid-acting insulin an alogue, insulin glulisine, is highly effective in controlling postprandial blood glucose irrespective of the time of administration (before or after meal), has no negative effect on weight, shows a good efficacy profile at different BMI and is likely to decrease the induced apoptosis of beta-cells. Nevertheless, only long-term practice and further prospective studies will answer the question of how important the characterictics of insulin glulisine are from the clinical point of view.