Diabetes mellitus is a major health problem with increasing prevalence at a global level. The discovery of insulin in the early 1900s represented a major breakthrough in diabetes management, with further milestones being subsequently achieved with the identification of glucagon-like peptide-1 (GLP-1) and the introduction of GLP-1 receptor agonists (GLP-1 RAs) in clinical practice. Moreover, the subcutaneous delivery of biotherapeutics is a well-established route of administration generally preferred over the intravenous route due to better patient compliance and prolonged drug absorption. However, current subcutaneous formulations of GLP-1 RAs present pharmacokinetic problems that lead to adverse reactions and treatment discontinuation. In this review, we discuss the current challenges of subcutaneous administration of peptide-based therapeutics and provide an overview of the formulations available for the different routes of administration with improved bioavailability and reduced frequency of administration.

糖尿病是一个主要的健康问题，在全球范围内患病率不断增加。 1900 年代初胰岛素的发现代表了糖尿病治疗的重大突破，随后通过胰高血糖素样肽 1 (GLP-1) 的鉴定和 GLP-1 受体激动剂 (GLP-1) 的引入实现了进一步的里程碑RA）在临床实践中。此外，生物治疗药物的皮下递送是一种成熟的给药途径，由于患者依从性更好并且药物吸收时间更长，通常优于静脉内途径。然而，目前的 GLP-1 RA 皮下制剂存在药代动力学问题，导致不良反应和治疗中断。在这篇综述中，我们讨论了基于肽的治疗剂皮下给药目前面临的挑战，并概述了可用于不同给药途径的制剂，这些制剂具有改善的生物利用度和降低的给药频率。