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已发表论文
基于药理机制的 GLP-1RAs 及 GLP-1/GIP 双受体激动剂的临床应用：综述
Authors Liu Z, Yu S, Jin X, Sheng L, YanMu MR, Gao J, Lu J, Lei T
Received 11 August 2025
Accepted for publication 15 November 2025
Published 22 November 2025 Volume 2025:19 Pages 10383—10409
DOI https://doi.org/10.2147/DDDT.S559919
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Anastasios Lymperopoulos
Zhao Liu,1 Shanshan Yu,1 Xinyan Jin,1 Luguang Sheng,2 Mai Re YanMu,1 Jie Gao,1 Jun Lu,1 Tao Lei1
1Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Surgical Intensive Care Unit (SICU), Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
Correspondence: Tao Lei, Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, People’s Republic of China, Email taolei_12@sina.com Jun Lu, Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, People’s Republic of China, Email lujundoctor@163.com
Abstract: This review provides a comprehensive examination of the clinical pharmacological mechanisms and broad therapeutic applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual receptor agonists targeting both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. GLP-1RAs exert their effects by stimulating insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through the activation of the GLP-1 receptor. These agents have demonstrated significant efficacy in the management of type 2 diabetes mellitus (T2DM) and obesity. Moreover, emerging evidence suggests that GLP-1RAs may confer cardiovascular protection, neuroprotective benefits, and positive effects on mental health. Dual GLP-1/GIP receptor agonists, such as tirzepatide, simultaneously activate both receptors, thereby potentiating glycemic control, promoting weight loss, and ameliorating metabolic dysfunction. This review also addresses recent advances in the development of other dual and triple receptor agonists. Distinct from prior reviews that predominantly focus on a single drug class or limited clinical indications, this article systematically contrasts the mechanistic pathways, therapeutic efficacy, and safety profiles of GLP-1RAs versus GLP-1/GIP dual receptor agonists. Notably, it integrates the most current evidence pertaining to novel domains, such as perioperative management, neuropsychiatric outcomes, and the innovation of multi-receptor agonists. This synthesis offers a timely and practical resource to inform clinical precision medicine and to guide future investigative efforts.
Keywords: GLP-1RAs, GLP-1/GIP dual receptor agonist, tirzepatide, clinical pharmacology, T2DM, obesity, neuroprotection
1Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Surgical Intensive Care Unit (SICU), Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
Correspondence: Tao Lei, Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, People’s Republic of China, Email taolei_12@sina.com Jun Lu, Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, People’s Republic of China, Email lujundoctor@163.com
Abstract: This review provides a comprehensive examination of the clinical pharmacological mechanisms and broad therapeutic applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual receptor agonists targeting both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. GLP-1RAs exert their effects by stimulating insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through the activation of the GLP-1 receptor. These agents have demonstrated significant efficacy in the management of type 2 diabetes mellitus (T2DM) and obesity. Moreover, emerging evidence suggests that GLP-1RAs may confer cardiovascular protection, neuroprotective benefits, and positive effects on mental health. Dual GLP-1/GIP receptor agonists, such as tirzepatide, simultaneously activate both receptors, thereby potentiating glycemic control, promoting weight loss, and ameliorating metabolic dysfunction. This review also addresses recent advances in the development of other dual and triple receptor agonists. Distinct from prior reviews that predominantly focus on a single drug class or limited clinical indications, this article systematically contrasts the mechanistic pathways, therapeutic efficacy, and safety profiles of GLP-1RAs versus GLP-1/GIP dual receptor agonists. Notably, it integrates the most current evidence pertaining to novel domains, such as perioperative management, neuropsychiatric outcomes, and the innovation of multi-receptor agonists. This synthesis offers a timely and practical resource to inform clinical precision medicine and to guide future investigative efforts.
Keywords: GLP-1RAs, GLP-1/GIP dual receptor agonist, tirzepatide, clinical pharmacology, T2DM, obesity, neuroprotection