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Over time, pharmacological engineering enabled: Short-acting injectables (e.g., exenatide) Long-acting once-weekly injectables (liraglutide, semaglutide) Multi-target incretin therapies (tirzepatide) Oral peptide formulations and now oral small molecules The most recent breakthrough is the development of orally available GLP-1 receptor agonists, including: Orforglipron (Lilly) Elecoglipron (AstraZeneca) These compounds eliminate the need for injection and could dramatically expand accessibility and adherence in obesity and diabetes populations

This work was supported by the Funds of National Natural Science Foundation of China (82060728), Guizhou Provincial Science and Technology Department (MS [2025-380], Thousand Talents Program), Talents of Guizhou Science and Technology Platform [2021]1350-009, Zunyi Science and Technology Bureau (HZ-2023-173, HZ-2023-09, [2024] No

This imbalance is hypothesized to contribute to dysfunctions in the reward system, potentially manifesting as anhedonia and other depressive symptoms 45 , a clinical observation that aligns with the psychiatric side effects noted in GLP-1 RAs therapy

Li M, Wu X, Liang Y, Zhang H, Wu J, Wang C, Xu J, Yu W, Sha H, Wang L, Deng J (2020) Chronic mercury poisoning causing back pain in spondyloarthritis: a case report