Diabetes Division, Katholisches Klinikum Bochum, St Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Diabetes Division, Katholisches Klinikum Bochum, St Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Lancet Diabetes Endocrinol. 2021 Aug;9(8):525-544. doi: 10.1016/S2213-8587(21)00113-3. Epub 2021 Jun 25.
Despite the successful development of new therapies for the treatment of type 2 diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors, the search for novel treatment options that can provide better glycaemic control and at reduce complications is a continuous effort. The present Review aims to present an overview of novel targets and mechanisms and focuses on glucose-lowering effects guiding this search and developments. We discuss not only novel developments of insulin therapy (eg, so-called smart insulin preparation with a glucose-dependent mode of action), but also a group of drug classes for which extensive research efforts have not been rewarded with obvious clinical impact. We discuss the potential clinical use of the salutary adipokine adiponectin and the hepatokine fibroblast growth factor (FGF) 21, among others. A GLP-1 peptide receptor agonist (semaglutide) is now available for oral absorption, and small molecules activating GLP-1 receptors appear on the horizon. Bariatric surgery and its accompanying changes in the gut hormonal milieu offer a background for unimolecular peptides interacting with two or more receptors (for GLP-1, glucose-dependent insulinotropic polypeptide, glucagon, and peptide YY) and provide more substantial glycaemic control and bodyweight reduction compared with selective GLP-1 receptor agonists. These and additional approaches will help expand the toolbox of effective medications needed for optimising the treatment of well delineated subgroups of type 2 diabetes or help develop personalised approaches for glucose-lowering drugs based on individual characteristics of our patients.
尽管已经成功开发了治疗 2 型糖尿病的新型疗法，如胰高血糖素样肽-1（GLP-1）受体激动剂和钠-葡萄糖共转运蛋白-2 抑制剂，但仍在不断寻找能够提供更好血糖控制并减少并发症的新型治疗选择。本综述旨在概述新型靶点和机制，并重点介绍指导这一研究和开发的降糖作用。我们不仅讨论了胰岛素治疗的新进展（例如，具有葡萄糖依赖性作用模式的所谓智能胰岛素制剂），还讨论了一类药物，尽管进行了广泛的研究，但并未产生明显的临床影响。我们讨论了有益的脂肪因子脂联素和肝源因子成纤维细胞生长因子（FGF）21 等的潜在临床应用。现在有 GLP-1 肽受体激动剂（司美格鲁肽）可口服吸收，并且能够激活 GLP-1 受体的小分子也即将面世。减肥手术及其伴随的肠道激素环境变化为与两个或多个受体（GLP-1、葡萄糖依赖性胰岛素释放肽、胰高血糖素和肽 YY）相互作用的单分子肽提供了背景，并与选择性 GLP-1 受体激动剂相比提供了更实质性的血糖控制和体重减轻。这些和其他方法将有助于扩大优化 2 型糖尿病明确亚组治疗所需的有效药物工具包，或帮助根据患者个体特征开发基于个体化的降糖药物方法。
