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中华肥胖与代谢病电子杂志 ›› 2025, Vol. 11 ›› Issue (01) : 11 -18. doi: 10.3877/cma.j.issn.2095-9605.2025.01.002

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新型减重药物的作用机制与研究进展
张源1, 张忠洋1, 谢杰斌1, 梁钿苑1, 余征航1, 任亦星1,()   
  1. 1. 637000 南充,川北医学院附属医院胃肠外一科
  • 收稿日期:2024-11-19 出版日期:2025-02-28
  • 通信作者: 任亦星
  • 基金资助:
    国家自然科学基金(82070535)四川省卫生健康委员会(23LCYJ031)川北医学院附属医院科研发展计划项目(2024PTZK011)川北医学院附属医院横向课题项目(2025HX03)

The mechanism of action and research progress of novel anti-obesity medications

Yuan Zhang1, Zhongyang Zhang1, Jiebin Xie1, Dianyuan Liang1, Zhenghang Yu1, Yixing Ren1,()   

  1. 1. Department of Gastrointestinal Surgery I,Affiliated Hospital of Sichuan North Medical College,Nanchong 637000,China
  • Received:2024-11-19 Published:2025-02-28
  • Corresponding author: Yixing Ren
引用本文:

张源, 张忠洋, 谢杰斌, 梁钿苑, 余征航, 任亦星. 新型减重药物的作用机制与研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(01): 11-18.

Yuan Zhang, Zhongyang Zhang, Jiebin Xie, Dianyuan Liang, Zhenghang Yu, Yixing Ren. The mechanism of action and research progress of novel anti-obesity medications[J/OL]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 11-18.

肥胖已成为一种全球流行的慢性代谢性疾病,对公共卫生构成严重威胁。传统减重药物的效果有限且副作用较多,而新型减重药物凭借其独特的作用机制和良好的安全性,为肥胖症的治疗提供了新的选择。本综述将介绍新型减重药物的背景及其在治疗肥胖中的重要性,详细阐述其作用机制、最新研究进展以及未来发展方向。

Obesity has become a globally prevalent chronic metabolic disease,posing a serious threat to public health.Traditional anti-obesity drugs have limited efficacy and numerous side effects,whereas new anti-obesity drugs,with their unique mechanisms of action and good safety profiles,offer new options for the treatment of obesity.This review will introduce the background of new anti-obesity drugs and their importance in the treatment of obesity,detailing their mechanisms of action,the latest research progress,and future development directions.

图1 新型减重药的机制与代表药物 注:GLP-1为胰高血糖素样肽-1;GIP为葡萄糖依赖性促胰岛素多肽;5-HT为5-羟色胺;GABA为γ-氨基丁酸;ActRII为活化素II型受体
表1 各种新型减重药物的对比
[1]
中国医疗保健国际交流促进会营养与代谢管理分会,中国营养学会临床营养分会,中华医学会糖尿病学分会,等.中国超重/肥胖医学营养治疗指南(2021) [J].中国医学前沿杂志(电子版),2021,13(11):1-55.
[2]
Wang Y,Zhao L,Gao L,et al.Health policy and public health implications of obesity in China [J].The Lancet Diabetes &Endocrinology,2021,9(7):446-461.
[3]
Phelps NH,Singleton RK,Zhou B,et al.Worldwide trends in underweight and obesity from 1990 to 2022:a pooled analysis of 3663 population-representative studies with 222 million children,adolescents,and adults [J].The Lancet,2024,403(10431):1027-1050.
[4]
Dong Z,Xu L,Liu H,et al.Comparative efficacy of five long-term weight loss drugs:quantitative information for medication guidelines[J].Obes Rev,2017,18(12):1377-1385.
[5]
Gadde KM,Atkins KD.The limits and challenges of antiobesity pharmacotherapy [J].Expert Opinion on Pharmacotherapy,2020,21(11):1319-1328.
[6]
Proietto J.Medicines for long-term obesity management [J].Australian Prescriber,2022,45(2):38-40.
[7]
Gabe MBN,Breitschaft A,Knop FK,et al.Effect of oral semaglutide on energy intake,appetite,control of eating and gastric emptying in adults living with obesity:A randomized controlled trial [J].Diabetes Obes Metab,2024,26(10):4480-4489.
[8]
Drucker DJ.Mechanisms of action and therapeutic application of glucagon-like peptide-1 [J].Cell Metab,2018,27(4):740-756.
[9]
Wilding JPH,Batterham RL,Calanna S,et al.Once-weekly semaglutide in adults with overweight or obesity [J].N Engl J Med,2021,384(11):989-1002.
[10]
Targher G,Mantovani A,Byrne CD.Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease[J].Lancet Gastroenterol Hepatol,2023,8(2):179-191.
[11]
Miyawaki K,Yamada Y,Ban N,et al.Inhibition of gastric inhibitory polypeptide signaling prevents obesity [J].Nature Medicine,2002,8(7):738-742.
[12]
Varol C,Zvibel I,Spektor L,et al.Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation [J].J Immunol,2014,193(8):4002-4009.
[13]
Samms RJ,Coghlan MP,Sloop KW.How may GIP enhance the therapeutic efficacy of GLP-1? [J].Trends Endocrinol Metab,2020,31(6):410-421.
[14]
Jastreboff AM,Aronne LJ,Ahmad NN,et al.Tirzepatide once weekly for the treatment of obesity [J].N Engl J Med,2022,387(3):205-216.
[15]
Tall Bull S,Nuffer W,Trujillo JM.Tirzepatide:A novel,first-in-class,dual GIP/GLP-1 receptor agonist [J].Journal of Diabetes and its Complications,2022,36(12):108332.
[16]
Gratsianskaya SE,Valieva ZS,Martynyuk TV.The achievements of the modern specific therapy of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension:focus on the stimulator of soluble guanylate cyclase riociguat [J].Ter Arkh,2020,92(9):77-84.
[17]
Flores-Costa R,Alcaraz-Quiles J,Titos E,et al.The soluble guanylate cyclase stimulator IW-1973 prevents inflammation and fibrosis in experimental non-alcoholic steatohepatitis [J].Br J Pharmacol,2018,175(6):953-967.
[18]
Bower RL,Hay DL.Amylin structure-function relationships and receptor pharmacology:implications for amylin mimetic drug development [J].Br J Pharmacol,2016,173(12):1883-1898.
[19]
Liberini CG,Boyle CN,Cifani C,et al.Amylin receptor components and the leptin receptor are co-expressed in single rat area postrema neurons [J].Eur J Neurosci,2016,43(5):653-661.
[20]
Ueda T,Ugawa S,Saishin Y,et al.Expression of receptor-activity modifying protein (RAMP) mRNAs in the mouse brain [J].Brain Res Mol Brain Res,2001,93(1):36-45.
[21]
Ludvik B,Lell B,Hartter E,et al.Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes [J].Diabetes,1991,40(12):1615-1619.
[22]
Boyle CN,Lutz TA,Le Foll C.Amylin - Its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity [J].Mol Metab,2018,8:203-210.
[23]
Furió-Novejarque C,Sala-Mira I,Díez JL,et al.A model of subcutaneous pramlintide pharmacokinetics and its effect on gastric emptying:Proof-of-concept based on populational data [J].Comput Methods Programs Biomed,2024,244:107968.
[24]
D'ascanio AM,Mullally JA,Frishman WH.Cagrilintide:A longacting amylin analog for the treatment of obesity [J].Cardiol Rev,2024,32(1):83-90.
[25]
Goto Y,Nomura M,Tanaka K,et al.Genetic interactions between activin type IIB receptor and Smad2 genes in asymmetrical patterning of the thoracic organs and the development of pancreas islets [J].Dev Dyn,2007,236(10):2865-2874.
[26]
Allen DL,Cleary AS,Speaker KJ,et al.Myostatin,activin receptor IIb,and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice [J].Am J Physiol Endocrinol Metab,2008,294(5):E918-E27.
[27]
Nunn E,Jaiswal N,Gavin M,et al.Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism [J].Mol Metab,2024,80:101880.
[28]
Kaur M,Misra S.Bimagrumab:an investigational human monoclonal antibody against activin type II receptors for treating obesity [J].J Basic Clin Physiol Pharmacol,2024,35(6):325-334.
[29]
Kumawat VS,Kaur G.Therapeutic potential of cannabinoid receptor 2 in the treatment of diabetes mellitus and its complications [J].Eur J Pharmacol,2019,862:172628.
[30]
Rohbeck E,Eckel J,Romacho T.Cannabinoid receptors in metabolic regulation and diabetes [J].Physiology (Bethesda),2021,36(2):102-113.
[31]
Lingvay I,Brown-Frandsen K,Colhoun HM,et al.Semaglutide for cardiovascular event reduction in people with overweight or obesity:SELECT study baseline characteristics [J].Obesity,2022,31(1):111-122.
[32]
Knop FK,Aroda VR,Do Vale RD,et al.Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1):a randomised,double-blind,placebo-controlled,phase 3 trial [J].Lancet,2023,402(10403):705-719.
[33]
Weghuber D,Barrett T,Barrientos-Pérez M,et al.Once-weekly semaglutide in adolescents with obesity [J].N Engl J Med,2022,387(24):2245-2257.
[34]
Kosiborod MN,Petrie MC,Borlaug BA,et al.Semaglutide in patients with obesity-related heart failure and type 2 diabetes [J].New England Journal of Medicine,2024,390(15):1394-1407.
[35]
Wilding JPH,Batterham RL,Davies M,et al.Weight regain and cardiometabolic effects after withdrawal of semaglutide:The STEP 1 trial extension [J].Diabetes,Obesity and Metabolism,2022,24(8):1553-1564.
[36]
Ryan DH,Lingvay I,Deanfield J,et al.Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial [J].Nature Medicine,2024,30(7):2049-2057.
[37]
Kosiborod MN,Abildstrøm SZ,Borlaug BA,et al.Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity [J].New England Journal of Medicine,2023,389(12):1069-1084.
[38]
Gao L,Huang H,Zhang L,et al.Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients [J].Exp Clin Endocrinol Diabetes,2022,130(6):358-367.
[39]
Chen K,Chen L,Shan Z,et al.Beinaglutide for weight management in Chinese individuals with overweight or obesity:A phase 3 randomized controlled clinical study [J].Diabetes,Obesity and Metabolism,2023,26(2):690-698.
[40]
Zimmermann T,Thomas L,Baader-Pagler T,et al.BI 456906:Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy [J].Mol Metab,2022,66:101633.
[41]
Le Roux CW,Steen O,Lucas KJ,et al.Glucagon and GLP-1 receptor dual agonist survodutide for obesity:a randomised,double-blind,placebo-controlled,dose-finding phase 2 trial [J].The Lancet Diabetes& Endocrinology,2024,12(3):162-173.
[42]
Ji L,Jiang H,An P,et al.IBI362 (LY3305677),a weekly-dose GLP-1 and glucagon receptor dual agonist,in Chinese adults with overweight or obesity:A randomised,placebo-controlled,multiple ascending dose phase 1b study [J].EClinicalMedicine,2021,39:101088.
[43]
Ji L,Jiang H,Cheng Z,et al.A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity [J].Nature Communications,2023,14(1):8289.
[44]
Ji L,Gao L,Jiang H,et al.Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity:A randomised,placebo-controlled,multiple-ascending-dose phase 1b trial [J].EClinicalMedicine,2022,54:101691.
[45]
Pratt E,Ma X,Liu R,et al.Orforglipron (LY3502970),a novel,oral non-peptide glucagon-like peptide-1 receptor agonist:A Phase 1a,blinded,placebo-controlled,randomized,single- and multipleascending-dose study in healthy participants [J].Diabetes Obes Metab,2023,25(9):2634-2641.
[46]
Wharton S,Blevins T,Connery L,et al.Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity [J].N Engl J Med,2023,389(10):877-888.
[47]
Lupianez-Merly C,Dilmaghani S,Vosoughi K,et al.Review article:Pharmacologic management of obesity - updates on approved medications,indications and risks [J].Alimentary Pharmacology &Therapeutics,2024,59(4):475-491.
[48]
Jastreboff AM,Kaplan LM,Frías JP,et al.Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial [J].New England Journal of Medicine,2023,389(6):514-526.
[49]
Enebo LB,Berthelsen KK,Kankam M,et al.Safety,tolerability,pharmacokinetics,and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management:a randomised,controlled,phase 1b trial[J].Lancet,2021,397(10286):1736-1748.
[50]
Li H,Yu G,Huang Q,et al.Efficacy and safety of GLP-1RAs for people with obesity:A systematic review based on RCT and Bayesian network meta-analysis [J].Biomed Pharmacother,2024,171:116150.
[51]
Jastreboff AM,Kaplan LM,Frías JP,et al.triple-hormone-receptor agonist retatrutide for obesity - a phase 2 trial [J].N Engl J Med,2023,389(6):514-526.
[52]
Grilo CM,Lydecker JA,Jastreboff AM,et al.Naltrexone/bupropion for binge-eating disorder:A randomized,double-blind,placebocontrolled trial [J].Obesity (Silver Spring),2023,31(11):2762-2773.
[53]
Onakpoya IJ,Lee JJ,Mahtani KR,et al.Naltrexone-bupropion(Mysimba) in management of obesity:A systematic review and metaanalysis of unpublished clinical study reports [J].Br J Clin Pharmacol,2020,86(4):646-667.
[54]
Greenway FL,Fujioka K,Plodkowski RA,et al.Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I):a multicentre,randomised,double-blind,placebo-controlled,phase 3 trial [J].Lancet,2010,376(9741):595-605.
[55]
Thomas B,Lindblad AJ,Luu T,et al.Naltrexone-bupropion for weight loss [J].Can Fam Physician,2023,69(9):627.
[56]
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) [J].中华内分泌代谢杂志,2024,40(7):545-564.
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