Injectable thermosensitive hydrogel-based sustained delivery system for anti-diabetic peptides in type 2 diabetes mellitus therapy: A review

Injectable thermosensitive hydrogels have emerged as a promising class of biomaterials for the sustained delivery of drug. These smart systems undergo a sol-gel phase transition in response to physiological temperature, enabling minimally invasive injection and the formation of an in situ drug depot capable of controlled and sustained drug release. In recent years, thermosensitive hydrogels have drawn increasing attention in type 2 diabetes mellitus (T2DM) therapy, offering enhanced patient adherence, stable glycemic control, and reduced injection frequency compared with conventional formulations. Importantly, beyond glucose lowering, several hydrogel-based incretin therapies-particularly GLP-1 receptor agonists and dual GIP/GLP-1 agonists-have demonstrated clinically significant body-weight reduction and improved metabolic outcomes, addressing both hyperglycemia and obesity, two core components of T2DM pathophysiology. This review summarizes the classification, polymer composition, and drug release mechanisms of thermosensitive hydrogels. Special emphasis is placed on their use in the sustained delivery of insulin, GLP-1 receptor agonists and dual GIP/GLP-1 agonists. These hydrogel-based depots have demonstrated prolonged pharmacological efficacy, while preserving drug bioactivity, minimizing burst release, and achieving superior improvements in glycemic control and providing superior body-weight management with GLP-1 receptor agonists-loaded thermosensitive hydrogels, as compared with conventional injectable regimens. Finally, the challenges and future prospects of thermosensitive hydrogel systems are discussed, including the need for improved formulation stability, scalable manufacturing, and regulatory translation. With continued interdisciplinary advancements, injectable thermosensitive hydrogels hold strong potential as next-generation, long-acting, and patient-friendly delivery platforms for comprehensive diabetes management, encompassing both glycemic control and body-weight reduction in T2DM patients.