Strategies to Enhance the Therapeutic Efficacy of GLP-1 Receptor Agonists through Structural Modification and Carrier Delivery

Diabetes is a metabolic disorder characterized by insufficient endogenous insulin production or impaired sensitivity to insulin. In recent years, a class of incretin-based hypoglycemic drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs), have attracted great attention in the management of type 2 diabetes mellitus (T2DM) due to their benefits, including stable glycemic control ability, a low risk of hypoglycemia, and weight reduction for patients. However, like other peptide drugs, GLP-1RAs face challenges such as instability, susceptibility to enzymatic degradation, and immunogenicity, which severely limit their clinical application. In recent years, various strategies have been developed to improve the bioavailability and therapeutic efficacy of GLP-1RAs, including structural modification and carrier-mediated delivery. This article briefly introduces the research and application status of several common GLP-1RAs and their limitations. Taking exendin-4 as an example, we focus on the research progress of improving bioavailability and therapeutic efficacy based on structural modification and carrier delivery strategies, aiming to provide reference for the development of new GLP-1RAs treatment systems.