Oral Insulin Product Hexyl-Insulin Monoconjugate 2 (HIM2) in Type 1 Diabetes Mellitus: The Glucose Stabilization Effects of HIM2

Abstract

This study was designed to determine plasma glucose and insulin levels after administration of three escalating doses of the oral insulin product hexyl-insulin monoconjugate 2 (HIM2) in fasting, insulin-deprived adult patients with type 1 diabetes. The study was also designed to assess the safety of the product. Sixteen patients with daily insulin requirements of 27-60 units and glycosylated hemoglobin levels of 5.8-11.1% completed the study. Patients' regular insulin regimens were discontinued at bedtime, and they fasted overnight. Blood glucose levels were stabilized overnight by intravenous insulin infusion. In the morning, intravenous insulin was discontinued 30 min prior to an oral dose of HIM2 (0.6, 0.8, or 1.0 mg/kg). A second oral dose of HIM2 was administered 120 min later. Plasma glucose and insulin levels were measured during a 240-min evaluation period after the first HIM2 dose. Identical HIM2 dosing and study procedures were repeated 1 week later with the same patients. Stable or declining plasma glucose levels were observed on 31 out of a total of 32 dosing days beginning at 20 min after the initial administration of HIM2. After plasma glucose levels declined or were stable for 30 min to 2 h, increases were observed for some patients. However, for the majority of patients (68.8%), plasma glucose levels were <150% of predose levels throughout the postdose evaluation period. Similar results were observed after repeating the study procedures 1 week later. Also, plasma glucose area under the concentration-time curves (AUCs) were inversely correlated with plasma insulin AUCs. HIM2 appeared to be safe and well-tolerated in this study; no episodes of symptomatic hypoglycemia were observed. Thus, HIM2 prevented the expected rise in plasma glucose concentrations in insulin-deprived adult patients with type 1 diabetes. The lack of hypoglycemic events in this exploratory study is encouraging and suggests that there may be less risk of severe hypoglycemia associated with HIM2 when compared with injectable insulin. The promising data in this study support the hypothesis that oral HIM2 reproduces the physiological pathway of insulin secreted by the pancreas - through the portal vein directly to the liver - suggesting a therapeutic advantage in the management of type 1 diabetes mellitus.

Effect of camel milk on glycemic control and insulin requirement in patients with type 1 diabetes: 2-years randomized controlled trial

“…The promising data in this study are in consistent with study conducted by Clement et al (2002) using oral insulin product. The significant reduction was observed in HbA1c levels in camel-milk receiving group (7.81-5.44%).…”

“…Among the alternative routes available for insulin delivery, oral administration is the most preferable, as it offers significant advantages in terms of therapeutic efficacy and patient acceptability. As orally delivered insulin undergoes a hepatic pass before entering the circulation, it has the potential to mimic the effects of pancreas-secreted insulin in terms of inhibition of hepatic gluconeogenesis (Lewis et al, 1996;Clement et al, 2002). Camel milk is one such alternative, as one of its proteins has many characteristics similar to insulin (Abu-Lehia et al, 1989), and it does not form coagulum in acidic environment, thus, safeguarding the viability of its components and making it available for absorption in intestine.…”

Oral Protein Therapy for the Future – Transport of Glycolipid-Modified Proteins: Vision or Fiction

“…This may be one reason why this approach has not reached clinical trials so far for the most attractive candidates for oral protein delivery in the long term, such as insulin. Alternatively, derivatization of polypeptide drugs by using polyethylene glycol [40] and their encapsulation in pHresponsive gels and films [41] or in enteric-coated capsules containing sodium salicylate [42] , which become gradually dissolved or leaky along passage in the gastrointestinal tract, have been reported to prevent their enzymatic degradation and to enhance their absorption [43] . A number of these promising approaches have been taken into the clinics.…”

Oral Protein and Peptide Drug Delivery

“…The product was effective in preventing the expected rise in plasma glucose concentrations in these patients. 88,89 Another exploratory study of this product assessed the postprandial glucoselowering effects in patients with type 2 diabetes. Single oral doses of the chemically modified insulin were as effective as subcutaneous regular insulin in controlling postprandial glycemia with respect to a number of parameters.…”