Naseralallah Lina, Aboujabal Bodoor
Pharmacy Department, Hamad Medical Corporation, Doha, Qatar.
School of Pharmacy, College of Medical and Dental Sciences, Sir Robert Aitken Institute for Medical Research, University of Birmingham, Birmingham, UK.
Expert Opin Pharmacother. 2023 Mar;24(4):407-418. doi: 10.1080/14656566.2023.2181074. Epub 2023 Feb 26.
Type 2 diabetes mellitus (T2DM) is one of the leading causes of morbidity and mortality. Peptide-based multi-targeting agonists represent a new paradigm in metabolic pharmacology as they manifest multiplexed pharmacological actions over mono-agonists. Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R) agonist that has been recently approved by the FDA. This review aims to summarize the available evidence on the discovery, pharmacology, pharmacokinetic, pharmacodynamic, efficacy, and safety of tirzepatide in the pharmacotherapy of T2DM.
We searched PubMed, Embase, and International Pharmaceutical Abstracts to identify relevant papers on tirzepatide use in T2DM. Clinical trial registries were also searched.
Tirzepatide improves glycemic control compared to baseline, placebo, and active comparators. It is also associated with weight reduction and an improvement in some, but not all, dyslipidemia, cardiovascular risk, and nonalcoholic steatohepatitis (NASH) biomarkers. Tirzepatide has a favorable safety profile with a low risk of hypoglycemia; however, adverse events such as gastrointestinal reactions were frequently reported and sometimes even led to therapy discontinuation. Future research should focus on investigating the role of tirzepatide in obesity, NASH, and cardio-renal benefits. Real-world observational studies are also needed to assess rare and long-term adverse events.
2型糖尿病（T2DM）是发病和死亡的主要原因之一。基于肽的多靶点激动剂代表了代谢药理学的一种新范式，因为它们比单激动剂表现出多重药理作用。替尔泊肽是一种新型的双重葡萄糖依赖性促胰岛素多肽受体（GIPR）和胰高血糖素样肽-1受体（GLP-1R）激动剂，最近已获得美国食品药品监督管理局（FDA）的批准。本综述旨在总结关于替尔泊肽在T2DM药物治疗中的发现、药理学、药代动力学、药效学、疗效和安全性的现有证据。
我们检索了PubMed、Embase和国际药学文摘，以识别有关替尔泊肽用于T2DM的相关论文。还检索了临床试验注册库。
与基线、安慰剂和活性对照相比，替尔泊肽可改善血糖控制。它还与体重减轻以及部分（而非全部）血脂异常、心血管风险和非酒精性脂肪性肝炎（NASH）生物标志物的改善有关。替尔泊肽具有良好的安全性，低血糖风险低；然而，胃肠道反应等不良事件经常被报道，有时甚至导致治疗中断。未来的研究应侧重于研究替尔泊肽在肥胖、NASH和心肾益处方面的作用。还需要开展真实世界观察性研究来评估罕见和长期不良事件。
