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Life sciences · Journal article
Theoretical and Natural Science · September 29, 2026
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In China, the proportion of adults with type 2 diabetes (T2DM) is as high as 12%, and half of the population is overweight or obese. Currently, Glucagon-like peptide-1 (GLP-1) drugs have significant pharmacological effects in weight loss and the treatment of T2DM. In terms of drug development, progress is gradually moving from single-target injectables toward oral small molecules, GLP-1/GIP/glucagon multi-target agonists, combination formulations, and long-acting formulations. This article mainly studies how semaglutide is able to significantly extend its half-life through structural modification, allowing it to be administered once a week. Finally, the study concluded that semaglutide prevents cleavage by the DPP-4 enzyme through modification at position 8, increases circulation area beyond the glomerular filtration rate through albumin binding at position 26, and ensures receptor affinity and albumin binding at position 34 to maintain the effects of the modification at position 26. These three aspects together significantly regulate and greatly extend the half-life. This kind of research provides a basis for designing long-acting GLP-1 receptor agonists. In the future, this modification strategy could be used to develop multi-target agonists, helping to improve and upgrade drugs for metabolic disease treatment.