[The role of insulin analogues in the current treatment of diabetes mellitus]

Abstract

Introduction: Ever since insulin was discovered by Banting and Best in 1921, all further researches in this field had been conducted with one goal: to find new insulin molecules which would provide better glycemic control with fewer side effects i.e. to mimic endogenous physiological insulin secretion.

Normal insulin secretion: In healthy individuals, endogenous insulin secretion can be classified as basal (which provides basal glucose homeostasis) and stimulated (as a response to a meal). Conventional insulin preparations--human insulin, have time-action profiles that cannot fully immitate endogenous insulin secretion, thus leading to postprandial hyperglicemia and high glycemic oscilations during the day. RAPID-ACTING ANALOGUES: Rapid acting analogues should have a time-action profile with onset of less than one hour, duration less than four hours, hypoglycemic potency equal or greater than that of human insulin, and similar effects in all patients. Two rapid action analogues, lispro and aspart are available.

Basal insulin analogues: The ideal basal insulin should provide slow and constant absorption, long half-life that would provide once daily dosing (or every other day), and peakless effect. Insulin glargine led to solubility at pH 4 and to slow absorption in neutral pH environment. Insulin detemir is a soluble insulin analogue with neutral pH and affinity to bind to serum albumin, thus gaining prolonged action.

Mitogenic influence: The mitogenic influence of insulin is due to the affinity to bind to IGF-I receptors. Following two-year administration of glargine in mice and rats, systemic carcinogenic potential was not found, though there were reports of hepatocellular carcinomas, which are frequently found in these animals.

Conclusion: In the last two decades, many trials have shown that unsatisfactory glycemic control leads to chronic complications in both types of diabetes. Using basal glucose level, postprandial glycemy and HbA1c as metabolic parameters, it has been proven that only strict glycemic control can lower the risk of developing complications. Discovery of insulin analogues (both rapid acting and basal) enables physicians to provide better glycoregulation and less hypoglycemic incidents to their patients.