Advances and challenges in pharmacotherapy for obesity in China_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Yutong ¹ , LIU Danlu ¹ , XU Jinghao ¹ , PU Yujie ¹ , DU Qiang ¹ , Mulusa Fumpa ¹ , Jason Widjaja ² , ZHANG Guixiang ² , DU Xiao ² , CHENG Zhong ² ,  WAN Qianyi ² ,  CHEN Yi ²

1. West China School of Medicine, Sichuan University, Chengdu 610041, P. R. China;
2. Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

WAN Qianyi, Email: wanqianyi@scu.edu.cn; CHEN Yi, Email: toddy@scu.edu.cn

Keywords：

obesity; weight-loss drugs; glucagon-like peptide-1 receptor agonists; multi-target therapy

DOI：

10.7507/1007-9424.202507084

Video：

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Abstract Full text Figures/Tables Video References Cited by

Obesity is a chronic metabolic disease driven by multiple factors such as genetic susceptibility, environmental factors, and neuroendocrine system disorders. In recent years, the prevalence of obesity in China has been increasing year by year, and a series of obesity-induced diseases are a serious threat to public health. Glucagon-like peptide-1 receptor agonists, as a representative of the new weight loss drugs, have shown a therapeutic effect close to that of weight-loss metabolic surgery in clinical trials by targeting central appetite and metabolism and other synergistic effects, but they still face key problems such as significant differences in individual efficacy, limited evidence of the safety of long-term treatment, and regaining body weight after discontinuation of the drug. The mechanism of action and clinical evidence of several obesity drugs approved and listed in China are summarized, and the progress and challenges of obesity drug therapy in China in combination with the progress of international cutting-edge multi-targeted drug research and development are discussed, with a view to providing a scientific basis for the clinical drug management of obesity, and to provide ideas for the research and development of obesity drugs in China as well as for the clinical transformation.

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1. 中华医学会内分泌学分会. 肥胖患者的长期体重管理及药物临床应用指南(2024版). 中华内分泌代谢杂志, 2024, 40(7): 545-564.
2. Shah N, Sanyal AJ. A pragmatic management approach for metabolic dysfunction-associated steatosis and steatohepatitis. Am J Gastroenterol, 2025, 120(1): 75-82.
3. Ndumele CE, Neeland IJ, Tuttle KR, et al. A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: A scientific statement from the American Heart Association. Circulation, 2023, 148(20): 1636-1664.
4. Chen J, Cai M, Zhan C. Neuronal regulation of feeding and energy metabolism: A focus on the hypothalamus and brainstem. Neurosci Bull, 2025, 41(4): 665-675.
5. Qiu J, Bosch MA, Stincic TL, et al. CRISPR/SaCas9 mutagenesis of stromal interaction molecule 1 in proopiomelanocortin neurons increases glutamatergic excitability and protects against diet-induced obesity. Mol Metab, 2022, 66: 101645. doi: 10.1016/j.molmet.2022.101645.
6. Tan HL, Yin L, Tan Y, et al. Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake. Nature, 2024, 636(8041): 198-205.
7. Roy P, Kant R, Kaur A, et al. Leptin resistance and cardiometabolic disorders: Bridging molecular pathways, genetic variants, and therapeutic innovation. Curr Cardiol Rev, 2025, 21(5): E1573403X356019. doi: 10.2174/011573403X356019250118170444.
8. Skoracka K, Hryhorowicz S, Schulz P, et al. The role of leptin and ghrelin in the regulation of appetite in obesity. Peptides, 2025, 186: 171367. doi: 10.1016/j.peptides.2025.171367.
9. Kamakura R, Raza GS, Sodum N, et al. Colonic delivery of nutrients for sustained and prolonged release of gut peptides: A novel strategy for appetite management. Mol Nutr Food Res, 2022, 66(19): e2200192. doi: 10.1002/mnfr.202200192.
10. McKnight AD, Alhadeff AL. Nutrient detection pathways for food reinforcement and satiation. Curr Opin Neurobiol, 2025, 92: 103040. doi: 10.1016/j.conb.2025.103040.
11. Zhang Z, Cui Y, Su V, et al. A PPARγ/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice. J Clin Invest, 2023, 133(21): e170072. doi: 10.1172/JCI170072.
12. Liu X, Zhang Z, Song Y, et al. An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications. Front Endocrinol (Lausanne), 2023, 13: 1065263. doi: 10.3389/fendo.2022.1065263.
13. Takeda Y, Harada Y, Yoshikawa T, et al. Mitochondrial energy metabolism in the regulation of thermogenic brown fats and human metabolic diseases. Int J Mol Sci, 2023, 24(2): 1352. doi: 10.3390/ijms24021352.
14. Zhao L, Li W, Zhang P, et al. Liraglutide induced browning of visceral white adipose through regulation of miRNAs in high-fat-diet-induced obese mice. Endocrine, 2024, 85(1): 222-232.
15. Hamjane N, Mechita MB, Nourouti NG, et al. Gut microbiota dysbiosis-associated obesity and its involvement in cardiovascular diseases and type 2 diabetes. A systematic review. Microvasc Res, 2024, 151: 104601. doi: 10.1016/j.mvr.2023.104601.
16. Yao Q, Yu Z, Meng Q, et al. The role of small intestinal bacterial overgrowth in obesity and its related diseases. Biochem Pharmacol, 2023, 212: 115546. doi: 10.1016/j.bcp.2023.115546.
17. Yarahmadi A, Afkhami H, Javadi A, et al. Understanding the complex function of gut microbiota: Its impact on the pathogenesis of obesity and beyond: A comprehensive review. Diabetol Metab Syndr, 2024, 16(1): 308. doi: 10.1186/s13098-024-01561-z.
18. Zhao Q, Han B, Xu Q, et al. Proteome and genome integration analysis of obesity. Chin Med J (Engl), 2023, 136(8): 910-921.
19. Berseneva A, Kovalenko E, Vergasova E, et al. Association of common genetic variants with body mass index in Russian population. Eur J Clin Nutr, 2023, 77(5): 574-578.
20. Ponce-Gonzalez JG, Martínez-Ávila Á, Velázquez-Díaz D, et al. Impact of the FTO gene variation on appetite and fat oxidation in young adults. Nutrients, 2023, 15(9): 2037. doi: 10.3390/nu15092037.
21. Li RL, Kang S. Rewriting cellular fate: Epigenetic interventions in obesity and cellular programming. Mol Med, 2024, 30(1): 169. doi: 10.1186/s10020-024-00944-2.
22. Vergnes L, Wiese CB, Zore T, et al. Gene regulation and mitochondrial activity during white and brown adipogenesis are modulated by KDM5 histone demethylase. J Endocr Soc, 2024, 8(4): bvae029. doi: 10.1210/jendso/bvae029.
23. Sjöström L. Analysis of the XENDOS study (Xenical in the prevention of diabetes in obese subjects). Endocr Pract, 2006, 12 Suppl 1: 31-33.
24. Shi YF, Pan CY, Hill J, et al. Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed type 2 diabetes. Diabet Med, 2005, 22(12): 1737-1743.
25. Gudzune KA, Kushner RF. Medications for obesity: A review. JAMA, 2024, 332(7): 571-584.
26. Uehira Y, Ueno H, Miyamoto J, et al. Impact of the lipase inhibitor orlistat on the human gut microbiota. Obes Res Clin Pract, 2023, 17(5): 411-420.
27. Grunvald E, Shah R, Hernaez R, et al. AGA clinical practice guideline on pharmacological interventions for adults with obesity. Gastroenterology, 2022, 163(5): 1198-1225.
28. Baccari MC, Vannucchi MG, Idrizaj E. The possible involvement of glucagon-like peptide-2 in the regulation of food intake through the gut-brain axis. Nutrients, 2024, 16(18): 3069. doi: 10.3390/nu16183069.
29. Moiz A, Filion KB, Tsoukas MA, et al. Mechanisms of GLP-1 receptor agonist-induced weight loss: A review of central and peripheral pathways in appetite and energy regulation. Am J Med, 2025, 138(6): 934-940.
30. Fathy MA, Alsemeh AE, Habib MA, et al. Liraglutide ameliorates diabetic-induced testicular dysfunction in male rats: Role of GLP-1/Kiss1/GnRH and TGF-β/Smad signaling pathways. Front Pharmacol, 2023, 14: 1224985. doi: 10.3389/fphar.2023.1224985.
31. Webster AN, Becker JJ, Li C, et al. Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety. Nat Metab, 2024, 6(12): 2354-2373.
32. Mashayekhi M, Nian H, Mayfield D, et al. Weight loss-independent effect of liraglutide on insulin sensitivity in individuals with obesity and prediabetes. Diabetes, 2024, 73(1): 38-50.
33. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3. 0 mg of liraglutide in weight management. N Engl J Med, 2015, 373(1): 11-22.
34. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: The SCALE diabetes randomized clinical trial. JAMA, 2015, 314(7): 687-699.
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