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GLP-1 激动剂的最新进展:当前的进展和挑战。

Recent updates on GLP-1 agonists: Current advancements & challenges.

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar 382355, Gujarat, India.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar 382355, Gujarat, India.

出版信息

Biomed Pharmacother. 2018 Dec;108:952-962. doi: 10.1016/j.biopha.2018.08.088. Epub 2018 Sep 27.

Abstract

Glucagon-like peptide (GLP)-1 is an incretin hormone exhibiting several pharmacological actions such as neuroprotection, increased cognitive function, cardio-protection, decreased hypertension, suppression of acid secretion, increase in lyposis, and protection from inflammation. The most potent actions are glucose-dependent insulinotropic and glucagonostatic actions, stimulation of β-cell proliferation, enhanced insulin secretion and reduced weight gain in patients with type-2 diabetes pertaining to blood glucose control. Despite all these actions, its short half-life (around 2∼min) and degradation by a dipeptidyl peptidase-4 enzyme (DPP-4) limits the therapeutic utility of GLP1. In this review, we have discussed DPP IV-resistant analogs of GLP-1 currently present in clinical trials such as Exenatide, Liraglutide, Semaglutide, Efpeglenatide, Exenatide ER, Ittca 650 (Intarcia), Dulaglutide, Albiglutide, and Lixisenatide. Moreover, we have also discussed in detail the pharmacology, signaling mechanisms, and pharmacokinetic properties (Cmax, Tmax, T Vd, and Bioavailability) of DPP IV-resistant analogs of (GLP-1). Interestingly, GLP-1 agonist drugs have shown better potential to treat type-2 diabetes mellitus (T2DM) as compared to currently used drugs in clinics without causing the side effects of hypoglycemia and weight gain.

摘要

胰高血糖素样肽 (GLP)-1 是一种肠促胰岛素激素,具有多种药理作用,如神经保护、认知功能增强、心脏保护、降低高血压、抑制胃酸分泌、脂肪增加和抗炎作用。最有效的作用是葡萄糖依赖性胰岛素促分泌和胰高血糖素抑制作用、刺激β细胞增殖、增强胰岛素分泌和降低 2 型糖尿病患者的体重增加,从而控制血糖。尽管有这些作用,但由于其半衰期短(约 2∼min)和二肽基肽酶-4 酶(DPP-4)降解,限制了 GLP1 的治疗用途。在这篇综述中,我们讨论了目前处于临床试验阶段的 GLP-1 的 DPP IV 抗性类似物,如 Exenatide、Liraglutide、Semaglutide、Efpeglenatide、Exenatide ER、Ittca 650(Intarcia)、Dulaglutide、Albiglutide 和 Lixisenatide。此外,我们还详细讨论了 DPP IV 抗性类似物(GLP-1)的药理学、信号转导机制和药代动力学特性(Cmax、Tmax、T Vd 和生物利用度)。有趣的是,与目前临床上使用的药物相比,GLP-1 激动剂药物在治疗 2 型糖尿病(T2DM)方面显示出了更好的潜力,而不会引起低血糖和体重增加等副作用。

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