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.

尽管已成功开发出治疗 2 型糖尿病的新疗法，例如胰高血糖素样肽 1 (GLP-1) 受体激动剂和钠-葡萄糖协同转运蛋白 2 抑制剂，但仍在寻找可提供更好血糖的新治疗方案。控制和减少并发症是一项持续的努力。本综述旨在概述新的靶点和机制，并侧重于指导这一研究和发展的降糖作用。我们不仅讨论了胰岛素治疗的新发展（例如，所谓的具有葡萄糖依赖性作用模式的智能胰岛素制剂），而且还讨论了大量研究工作尚未获得明显临床影响的药物类别。我们讨论了有益的脂肪因子脂联素和肝因子成纤维细胞生长因子 (FGF) 21 等的潜在临床用途。一种 GLP-1 肽受体激动剂（semaglutide）现在可用于口服吸收，激活 GLP-1 受体的小分子即将出现。减肥手术及其伴随的肠道激素环境变化为单分子肽与两种或多种受体（GLP-1、葡萄糖依赖性促胰岛素多肽、胰高血糖素和肽 YY）相互作用提供了背景，并提供了更实质性的血糖控制和体重减轻与选择性 GLP-1 受体激动剂相比。