ABSTRACT

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP4is) exert their effects via the incretin system, which augments glucose-dependent insulin secretion in response to nutrient intake (the ‘incretin effect’). Both classes are well-established pharmacologic options for the management of glycemic control in individuals with type 2 diabetes (T2D) after failure of first-line metformin; however, they have inherent differences in their mechanisms of action that are reflected in their clinical safety and efficacy profiles. GLP-1RAs have high glycemic efficacy and are associated with weight loss and, in some cases, cardioprotective effects, with a side-effect profile of predominantly transient gastrointestinal adverse events. Most GLP-1RAs are administered as subcutaneous injection, although an oral formulation of one GLP-1RA, semaglutide, has recently become available. DPP4is provide moderate glycemic control, are weight-neutral, and do not offer any cardiovascular benefits, but are generally well tolerated. DPP4is are all administered orally. This narrative review aims to provide guidance for a primary care audience on the similarities and differences between GLP-1RA and DPP4i therapies, with a focus on their mechanism of action, clinical safety, efficacy, and real-world effectiveness. The role of incretin-based therapies in the T2D treatment paradigm, including key considerations for guiding treatment decisions, will also be discussed.

摘要

胰高血糖素样肽 1 受体激动剂 (GLP-1RAs) 和二肽基肽酶 4 抑制剂 (DPP4is) 通过肠促胰岛素系统发挥作用，肠促胰素系统增加葡萄糖依赖性胰岛素分泌以响应营养摄入（“肠促胰岛素效应”）。这两类药物都是用于在一线二甲双胍治疗失败后管理 2 型糖尿病 (T2D) 患者血糖控制的成熟药物选择；然而，它们的作用机制存在固有差异，这反映在它们的临床安全性和有效性特征中。GLP-1RAs 具有高升糖功效，与体重减轻有关，在某些情况下，还有心脏保护作用，副作用主要是短暂的胃肠道不良事件。大多数 GLP-1RA 以皮下注射方式给药，尽管最近有一种 GLP-1RA 的口服制剂 semaglutide 可用。DPP4is 提供适度的血糖控制，体重中性，不提供任何心血管益处，但通常耐受性良好。DPP4is 都是口服给药。这篇叙述性综述旨在为初级保健受众提供 GLP-1RA 和 DPP4i 疗法之间异同的指导，重点是它们的作用机制、临床安全性、有效性和现实世界的有效性。还将讨论基于肠促胰素的疗法在 T2D 治疗范式中的作用，包括指导治疗决策的关键考虑因素。但通常耐受性良好。DPP4is 都是口服给药。这篇叙述性综述旨在为初级保健受众提供 GLP-1RA 和 DPP4i 疗法之间异同的指导，重点是它们的作用机制、临床安全性、有效性和现实世界的有效性。还将讨论基于肠促胰素的疗法在 T2D 治疗范式中的作用，包括指导治疗决策的关键考虑因素。但通常耐受性良好。DPP4is 都是口服给药。这篇叙述性综述旨在为初级保健受众提供 GLP-1RA 和 DPP4i 疗法之间异同的指导，重点是它们的作用机制、临床安全性、有效性和现实世界的有效性。还将讨论基于肠促胰素的疗法在 T2D 治疗范式中的作用，包括指导治疗决策的关键考虑因素。