Continuation Of Insulin Therapy for Diabetics
Linjeta™, formally called VIAject®, is recombinant human insulin with a fast onset of action. In a study of pharmacodynamics and pharmacokinetic properties of an ultrafast insulin, it was found to have an earlier onset of action and shorter time to maximal plasma insulin concentration. VIAject®, compared to human insulin, had less within-subject variability of plasma insulin. In a double blind, three-way crossover study with VIAject® compared to lispro insulin, VIAject® was found to be bioequivalent to the previously used formulation and had a faster absorption/onset of action than insulin lispro.
VIAject® is currently undergoing two pivotal phase 3 clinical studies for both type 1 and type 2 diabetes. Since the VIAject® pharmacodynamics mimic 1st phase release insulin and the amount of insulin circulating several hours after a meal, it leads to possible reduction in hypoglycemia, and it is predicted to possibly prevent weight gain. Artificial pancreas: Closed-loop insulin delivery is an emerging therapeutic approach for people with type 1 diabetes. Even with the use of continuous glucose monitors and insulin pumps, most people with type 1 diabetes do not achieve glycemic goals and continue to have unacceptable rates of hypoglycemia.
The goal of closed-loop therapy is to achieve good glycemic control with the use of a control algorithm that directs insulin delivery according to glucose levels while reducing the risk of hypoglycemia. Insulin delivery in the closed-loop system is modulated at intervals of 1-15 minutes, depending on interstitial glucose levels. The uniqueness of this approach is the real-time response of insulin delivery to the glucose levels, similar to that of the beta-cell. The algorithms that are most relevant include the proportionalintegral-derivative control (PID) and the model-predictive control (MPC). Several areas need improvement to have a near normal closed-loop system. First and foremost is the rapid onset of action. The lag period of current fast-acting insulin analogs is 90-120 minutes. Current trials show promise. In a phase 2 study with or without recombinant human hyaluronidase (rHuPH20) that accelerates insulin absorption in healthy volunteers, both lispro and recombinant human insulin with rHuPH20 produced earlier and greater peak insulin concentrations, improved postprandial glycemic control, and reduced hypoglycemia. Rapid acting insulins are being developed that use monomeric insulins that cannot form hexamers.
As mentioned earlier, ultrafast insulin VIAject®, a formulation of human soluble insulin, improves the rate of insulin absorption. It has been reported in a study to evaluate its pharmacodynamics and pharmacokinetic properties that VIAject® has higher metabolic activity in the first two hours after injection. True closed-loop systems, which determine minute-to-minute insulin delivery based on continuous glucose sensor data in real time, have shown promise in small inpatient feasibility studies using a variety of algorithmic and hormonal approaches. Buccal delivery of insulin: The buccal delivery system for insulin delivers insulin through an aerosol spray into the oral cavity and hence differs from inhalers. The insulin is absorbed through the inside of the cheeks and in the back of the mouth instead of the lungs. In vivo studies performed on diabetic rats showed promising results with stable blood glucose profile with a significant hypoglycemic response after 7 hours using buccal insulin. Similar studies in the rabbit and rat have shown that buccal spray of insulin is an effective insulin delivery system, which is promising for clinical trial and future clinical application. Though promising in rat models, they are not appropriate models because rats have a keratinized buccal mucosa. The only animal models with comparable human buccal permeability are pigs.
(to be continue..)
