Mazdutide is a long-acting dual agonist of the glucagon-like peptide-1 receptor (GLP-1R; Ki=28.6nM) and the glucagon receptor (GCGR; Ki=17.7nM)[1-2]. Mazdutide can suppress appetite and slow gastric emptying by activating the GLP-1 receptor to reduce energy intake, while simultaneously increasing energy expenditure and promoting hepatic fat breakdown by activating the GCG receptor to improve metabolism. Mazdutide is used for the long-term management of adult overweight/obesity and the treatment of type 2 diabetes[3-4].
In vivo, db/db mice were subcutaneously administered Mazdutide (50-200μg/kg) once every three days for 12 consecutive weeks. Mazdutide significantly improved diabetes-associated cognitive dysfunction[5]. C57BL/6J male mice with obesity induced by a 13-week high-fat diet were subcutaneously administered Mazdutide (15nmol/kg) once every three days for 4 weeks. Mazdutide significantly reduced hepatic fat accumulation, and its effect was superior to that of a GLP-1R mono-agonist[6].
References:
[1] Shirley M. Mazdutide: First Approval. Drugs. 2025 Dec;85(12):1621-1627.
[2] Pan XF, Fang ZZ, Zhang L, et al. Obesity in China: current progress and future prospects. Lancet Diabetes Endocrinol. 2026 Feb;14(2):178-186.
[3] Bailey CJ, Flatt PR, Conlon JM. Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. Peptides. 2025 May;187:171380.
[4] Sidrak WR, Kalra S, Kalhan A. Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article. Indian J Endocrinol Metab. 2024 Sep-Oct;28(5):445-460.
[5] Dong W, Bai J, Yuan Q, Z, et al. Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis. EBioMedicine. 2025 Jul;117:105791.
[6] Xia H, Min Y, Wang Y, et al. Multiparametric MRI Evaluation of Liver Fat and Iron after Glucagon-like Peptide-1 Receptor and Glucagon Receptor Dual-Agonist Treatment in a High-Fat Diet-induced Mouse Model. Radiology. 2025 Aug;316(2):e243780.
Mazdutide是一种有长效作用的胰高血糖素样肽-1受体（GLP-1R；Ki=28.6nM）和胰高血糖素受体（GCGR；Ki=17.7nM）双重激动剂[1-2]。Mazdutide可通过激活GLP-1受体抑制食欲、延缓胃排空以减少能量摄入，同时通过激活GCG受体增加能量消耗、促进肝脏脂肪分解以改善代谢。Mazdutide可用于成人超重/肥胖的长期体重管理和2型糖尿病的治疗[3-4]。
在体内，Mazdutide（50-200μg/kg）每三天一次皮下注射，用于处理的db/db小鼠，连续12周。Mazdutide显著改善了糖尿病相关的认知功能障碍[5]。Mazdutide（15nmol/kg）每三天一次皮下注射，用于处理经13周高脂饮食诱导的C57BL/6J雄性肥胖小鼠，持续4周。Mazdutide显著减少了肝脏脂肪积累，且效果优于GLP-1R单激动剂[6]。