Department of Life Sciences, International Medical University, Kuala Lumpur, Malaysia.
School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.
Panminerva Med. 2018 Sep;60(3):117-131. doi: 10.23736/S0031-0808.18.03455-9. Epub 2018 Apr 24.
The prevalence of type 2 diabetes mellitus (T2DM) has been increasing at an alarming rate. With an increased understanding of the pathophysiology and pathogenesis of T2DM, various new therapeutic options have been developed to target different key defects in T2DM. Incremental innovations of existing therapies either through unprecedented drug combinations, modified drug molecules, or improved delivery systems are capable to nullify some of the undesirable side effects of traditional therapies as well as to enhance effectiveness. The existing administration routes include inhalation, nasal, buccal, parenteral and oral. Newer drug targets such as protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), sirtuin (SIRT), and others are novel approaches that act via different mechanisms and possibly treating T2DM of distinct variations and aetiologies. Other therapies such as endobarrier, gene therapy, and stem cell technology utilize advanced techniques to treat T2DM, and the potential of these therapies are still being explored. Gene therapy is plausible to fix the underlying pathology of T2DM instead of using traditional reactive treatments, especially with the debut of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein9 (CRISPR-Cas9) gene editing tool. Molecular targets in T2DM are also being extensively studied as it could target the defects at the molecular level. Furthermore, antibody therapies and vaccinations are also being developed against T2DM; but the ongoing clinical trials are relatively lesser and the developmental progress is slower. Although, there are many therapies designed to cure T2DM, each of them has their own advantages and disadvantages. The preference for the treatment plan usually depends on the health status of the patient and the treatment goal. Therefore, an ideal treatment should take patient's compliance, efficacy, potency, bioavailability, and other pharmacological and non-pharmacological properties into account.
2 型糖尿病(T2DM)的患病率正在以惊人的速度增长。随着对 T2DM 病理生理学和发病机制的深入了解,已经开发出各种新的治疗方法来针对 T2DM 的不同关键缺陷。通过前所未有的药物组合、改良的药物分子或改进的给药系统,对现有治疗方法进行渐进式创新,既能消除传统治疗方法的一些不良副作用,又能提高疗效。现有的给药途径包括吸入、鼻内、口腔颊、胃肠外和口服。新型药物靶点如蛋白激酶 B(Akt/PKB)、AMP 激活的蛋白激酶(AMPK)、sirtuin(SIRT)等是通过不同机制作用的新方法,可能治疗不同变异和病因的 T2DM。其他治疗方法,如内屏障、基因治疗和干细胞技术,利用先进技术治疗 T2DM,这些治疗方法的潜力仍在探索中。基因治疗有可能修复 T2DM 的潜在病理学,而不是使用传统的反应性治疗方法,特别是随着 Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein9 (CRISPR-Cas9) 基因编辑工具的问世。T2DM 中的分子靶点也在被广泛研究,因为它可以针对分子水平的缺陷。此外,针对 T2DM 的抗体治疗和疫苗也在开发中;但正在进行的临床试验相对较少,开发进展较慢。尽管有许多旨在治疗 T2DM 的疗法,但每种疗法都有其自身的优缺点。治疗方案的选择通常取决于患者的健康状况和治疗目标。因此,理想的治疗方法应考虑患者的依从性、疗效、效力、生物利用度以及其他药理学和非药理学特性。