Joshi Clinic and Lilavati Hospital, Mumbai, Maharashtra, India.
Biocon Biologics Ltd, Biocon House, Semicon Park, Electronic City Phase 2, Bengaluru, Karnataka, 560100, India.
Drugs. 2023 Sep;83(13):1161-1178. doi: 10.1007/s40265-023-01925-1. Epub 2023 Aug 14.
Insulin therapy is indispensable for achieving glycemic control in all patients with type 1 diabetes mellitus and many patients with type 2 diabetes mellitus. Insulin injections are associated with negative connotations in patients owing to administration discomfort and adverse effects such as hypoglycemia and weight gain. Insulin administered orally can overcome these limitations by providing a convenient and effective mode of delivery with a potentially lower risk of hypoglycemia. Oral insulin mimics the physiologic process of insulin secretion, absorption into the portal circulation, and subsequent peripheral delivery, unlike the subcutaneous route that results in peripheral hyperinsulinemia. Insulin tregopil (IN-105), a new generation human recombinant insulin, methoxy (polyethylene glycol) hexanoyl human recombinant insulin, is developed by Biocon as an ultra-fast onset short-acting oral insulin analog. This recombinant oral insulin is a single short-chain amphiphilic oligomer modified with the covalent attachment of methoxy-triethylene-glycol-propionyl moiety at Lys-β-amino group of the B-chain via an amide linkage. Sodium caprate, an excipient in the insulin tregopil formulation, is a permeation enhancer that increases its absorption through the gastrointestinal tract. Also, meal composition has been shown to non-significantly affect its absorption. Several global randomized, controlled clinical trials have been conducted in type 1 and type 2 diabetes patients towards the clinical development of insulin tregopil. The formulation shows post-prandial glucose control that is more effective than placebo throughout the meal period; however, compared with an active comparator insulin aspart, the post-prandial control is more effective mainly in the early post-meal period. It shows a good safety profile with a lower incidence of clinically significant hypoglycemia. This review covers the overall clinical development of insulin tregopil establishing it as an ultra-fast onset, short-acting oral insulin analog for optimizing post-prandial glucose.
胰岛素治疗对于所有 1 型糖尿病患者和许多 2 型糖尿病患者实现血糖控制都是不可或缺的。由于注射胰岛素会引起不适和低血糖、体重增加等不良反应，因此患者对胰岛素治疗存在负面看法。口服胰岛素可以通过提供一种方便有效的给药方式来克服这些限制，同时低血糖风险可能更低。口服胰岛素模拟了胰岛素分泌、门静脉吸收和随后的外周输送的生理过程，而不同于导致外周高胰岛素血症的皮下途径。IN-105（胰岛素 tregopil）是新一代人重组胰岛素，是 Biocon 公司开发的一种超快速起效的短效口服胰岛素类似物。这种重组口服胰岛素是一种单链短链两亲性低聚物，通过酰胺键将甲氧基-三乙二醇-丙酰基部分共价连接到 B 链的β-氨基赖氨酸上进行修饰。胰岛素 tregopil 配方中的赋形剂癸酸钠是一种渗透增强剂，可通过胃肠道增加其吸收。此外，膳食成分已被证明对其吸收没有显著影响。已经在 1 型和 2 型糖尿病患者中进行了几项全球随机对照临床试验，以推进胰岛素 tregopil 的临床开发。该配方在整个进餐期间显示出比安慰剂更有效的餐后血糖控制；然而，与活性对照胰岛素门冬氨酸相比，餐后控制在进餐早期更为有效。它具有良好的安全性，临床显著低血糖的发生率较低。本综述涵盖了胰岛素 tregopil 的整体临床开发，确立了它作为一种超快速起效、短效的口服胰岛素类似物，可优化餐后血糖。
