Long‐Acting Hydrogel‐Based Depot Formulations of Tirzepatide and Semaglutide for the Management of Type 2 Diabetes and Weight

ABSTRACT Several incretin hormone therapies have been clinically approved and have revolutionized the treatment of diabetes and obesity. Promising therapeutics include semaglutide (Ozempic and Wegovy), a glucagon‐like peptide‐1 (GLP‐1) receptor agonist, and tirzepatide (Mounjaro), a dual agonist for GLP‐1 and glucose‐dependent insulinotropic polypeptide (GIP) receptors. These molecules help regulate blood glucose levels, enhance insulin secretion and sensitivity, and reduce appetite. Currently, these treatments require weekly injections, which can be challenging for patients to adhere to. We previously reported the development of an injectable hydrogel depot technology enabling months‐long release of semaglutide (Sema). Here, we further developed this technology for improved prolonged release of both Sema and tirzepatide (TZP). In a type 2 diabetes rat model, we show that a single administration of hydrogel‐based formulations of either Sema or TZP maintained relevant drug levels for over 6 weeks. In these studies, single administrations of long‐acting hydrogel‐based therapies of Sema or TZP were similarly effective at regulating blood glucose and weight compared to daily injections of either Sema or TZP in standard aqueous vehicles. This injectable hydrogel depot is easy to manufactureand exhibits excellent biocompatibility, enabling months‐long treatments with the potential to improve the management of diabetes and weight.