Since the discovery of insulin, continuous developments of this peptide have led to better management of diabetes mellitus, thus leading to a decrease in diabetes-related mortality. Despite these developments, we have seen an increase in diabetes cases, which has further necessitated more innovative methods for diabetes management. The subcutaneous administration of insulin remains the mainstay therapy for type 1 diabetes mellitus. However, despite the availability of insulin analogues with improved pharmacokinetics, challenges with conventional administration exist. The challenges associated with insulin injections include hypoglycaemic episodes, needle phobia, and injection-site inflammation, which all have been reported to reduce patient compliance. Ongoing research on diabetes management strives to develop therapies that provide improved glycaemic control with minimal side effects. In part, for these reasons, we have seen an increase in the search and development of alternative insulin delivery systems that are envisaged to circumvent the shortfalls associated with the conventional administration route. Several alternative drug delivery systems, such as oral, pulmonary, buccal, nasal, and transdermal, have been explored in the last century. These efforts have not been without victory, as we have seen the emergence of pulmonary (Exubera and Afrezza) and buccal insulin delivery systems licenced for therapeutic use. Despite the success seen in these two systems, their marketability and popularity have been severely compromised due to reported safety concerns. Although oral insulin delivery has always shown promise in the past decades; however, it was only limited to preclinical trials. The main challenge associated with this delivery route is poor bioavailability, which necessitates high insulin concentration to be administered. Due to recent developments, oral insulin has reached phase 3 clinical trials. It is believed that patients would prefer oral insulin as their preference is often observed for oral antidiabetics over injected ones. In the last decade, transdermal insulin has also gained interest, where delivery of insulin with a concomitant reduction in blood glucose concentration has been demonstrated in vivo. However, at present, there are no clinical studies that have reported the efficacy of transdermal insulin administration. With technological advancement, there is a potential to develop yet another insulin delivery system that would likely enter the markets. As these novel delivery systems have been found to be effective, emerging competing products should be welcome and appreciated.

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庆祝胰岛素发现百年：对新兴替代胰岛素输送系统的批判性评价

自从发现胰岛素以来，这种肽的不断发展导致了对糖尿病的更好管理，从而降低了与糖尿病相关的死亡率。尽管取得了这些进展，但我们已经看到糖尿病病例有所增加，这进一步需要更多创新的糖尿病管理方法。皮下注射胰岛素仍然是 1 型糖尿病的主要治疗方法。然而，尽管可获得药代动力学得到改善的胰岛素类似物，但传统给药仍存在挑战。与胰岛素注射相关的挑战包括低血糖发作、针头恐惧症和注射部位炎症，据报道，这些都会降低患者的依从性。正在进行的糖尿病管理研究致力于开发能够改善血糖控制且副作用最小的疗法。部分地，由于这些原因，我们已经看到了对替代胰岛素输送系统的研究和开发的增加，这些系统被设想用于规避与传统给药途径相关的不足。上个世纪已经探索了几种替代药物递送系统，例如口服、肺部、口腔、鼻腔和透皮。这些努力并非没有胜利，因为我们已经看到肺部（Exubera 和 Afrezza）和口腔胰岛素输送系统的出现获得了治疗用途的许可。尽管这两个系统取得了成功，但由于报告的安全问题，它们的适销性和受欢迎程度受到了严重损害。尽管口服胰岛素给药在过去几十年一直显示出希望；然而，它仅限于临床前试验。与这种递送途径相关的主要挑战是生物利用度差，这需要使用高浓度的胰岛素。由于最近的发展，口服胰岛素已进入 3 期临床试验阶段。据信，患者更喜欢口服胰岛素，因为经常观察到他们更喜欢口服抗糖尿病药而不是注射抗糖尿病药。在过去的十年中，透皮胰岛素也引起了人们的兴趣，其中已经在体内证明了胰岛素的递送伴随着血糖浓度的降低。但目前尚无临床研究报道经皮胰岛素给药的疗效。随着科技的进步，有可能开发出另一种可能进入市场的胰岛素输送系统。由于已发现这些新颖的递送系统是有效的，因此应该欢迎和赞赏新兴的竞争产品。