The search for analogues of insulin
Insulin analogues could improve the pharmacokinetic and pharmacodynamic characteristics of subcutaneously injected formulations. The aim is to mimic healthy endogenous insulin secretion.
With bolus insulin (e.g., insulin lispro, insulin aspart or insulin glulisine), absorption is more rapid and the peak is reached more quickly. Faster aspart and insulin urli reach even faster absorption through the addition of absorption enhancers. Prolonged absorption with an ideally flat profile for improved coverage of basal needs is obtained with formulations such as insulin glargine, insulin glargine u300, insulin detemir and insulin degludec.
Despite the existence of these promising compounds, there are still unmet needs and the pharmacokinetic and pharmacodynamic profiles could be improved even further. For example, although rapid-acting insulin analogues exhibit an earlier onset of action compared to short-acting human insulin, the absorption profile is slower than the physiological response to increased blood glucose. Furthermore, current insulin formulations demonstrate a relatively long duration of action, in particular at high doses, which creates a risk of hypoglycemia.
Long-acting insulin products should ideally present with a flat pharmacokinetic and pharmacodynamic profile and have a duration of action of 24 hours to cover the daily basal insulin needs.
Having been involved in the development of all commercially available insulin preparations, Profil has many years of experience in investigating the pharmacokinetics and pharmacodynamics of novel insulin analogues. We support sponsors in finding the optimal trial design to fulfill regulatory needs for first-in-human studies, proof-of-concept studies or bioequivalence trials.