切换至 "中华医学电子期刊资源库"

中华肥胖与代谢病电子杂志 ›› 2025, Vol. 11 ›› Issue (01) : 33 -39. doi: 10.3877/cma.j.issn.2095-9605.2025.01.005

专家论坛

基于营养刺激激素受体靶点新型减重药物的临床研究现状与进展
宋宇佳1, 孟化2,()   
  1. 1. 100069 北京,首都医科大学
    2. 100029 北京,中日友好医院普外科代谢减重中心
  • 收稿日期:2024-11-20 出版日期:2025-02-28
  • 通信作者: 孟化
  • 基金资助:
    国家自然科学基金面上项目(82470857)中日友好医院中央高水平医院临床科研业务费资助(2023-NHLHCRF-YS-0103)中日友好医院中央高水平医院临床科研业务费资助(2023-NHLHCRF-YYPP-TS-02)北京市研究型病房建设临床研究项目(2022-YJXBF-03-02)北京市自然科学基金面上项目(7242125)中日友好医院人才引进项目(No.2018-RC-1)青海省“昆仑英才·高端创新创业人才”项目(202308210043)

Clinical research status and progress of novel anti-obesity medications targeting nutrient-stimulatory hormone receptors

Yujia Song1, Hua Meng2,()   

  1. 1. Capital Medical University,Beijing,100069,China
    2. Obesity and Metabolic Disease Center,Department of General Surgery,China-Japan Friendship Hospital,Beijing,100029,China
  • Received:2024-11-20 Published:2025-02-28
  • Corresponding author: Hua Meng
引用本文:

宋宇佳, 孟化. 基于营养刺激激素受体靶点新型减重药物的临床研究现状与进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(01): 33-39.

Yujia Song, Hua Meng. Clinical research status and progress of novel anti-obesity medications targeting nutrient-stimulatory hormone receptors[J/OL]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 33-39.

全球肥胖发病率快速升高,中国肥胖问题日益严重,肥胖作为一种慢性、复发性的复杂疾病,严重危害肥胖患者的健康寿命以及生活质量。基于营养刺激激素(NuSH)受体靶点的新型减重药物为肥胖管理提供了减重手术以外的选择,成为生活方式干预基础上重要的辅助治疗手段。根据临床试验结果,新型减重药物具有显著的减重效果,同时可以改善2型糖尿病、心血管疾病以及其他肥胖相关合并症,其安全性也已得到证实。如今,已有4种新型减重药物在中国被批准用于体重管理,同时还有多种新型减重药物进入临床Ⅲ期试验。但目前,新型减重药物在临床试验和应用上仍存在一些有待解决的问题。未来随着这些问题逐步解决,更好的减重效果、更个性化的选择以及更多样的使用方式,将使新型减重药物在肥胖管理领域发挥出更大的潜能。

The global prevalence of obesity has escalated at an alarming rate,with China facing an increasingly critical obesity crisis.Recognized as a chronic,relapsing,and multifaceted disease,obesity significantly compromises both the health span and quality of life of those affected.New anti-obesity agents that target the nutrient-stimulated hormone (NuSH) receptor offer a promising alternative to bariatric surgery,serving as a vital adjunct to lifestyle interventions.Clinical trials have demonstrated that these novel therapies not only achieve substantial weight reduction but also improve outcomes in type 2 diabetes,cardiovascular disease,and other obesity-related comorbidities,with their safety profiles well-established.To date,four new weight-loss medications have received approval for weight management in China,and several others are advancing through Phase Ⅲ clinical trials.Nonetheless,there remain challenges to be addressed in the clinical evaluation and application of these therapies.Looking ahead,as these challenges are progressively overcome,the potential for enhanced weight-loss outcomes,more personalized treatment options,and diverse therapeutic applications will enable these novel weight-loss drugs to play an increasingly significant role in the management of obesity.

[1]
世界肥胖联盟.2024年世界肥胖报告 [EB/OL].伦敦:世界肥胖联盟,2024.https://data.worldobesity.org/publications/?cat=22
[2]
Peng W,Chen SQ,Chen XG,et al.Trends in major noncommunicable diseases and related risk factors in China 2002-2019:an analysis of nationally representative survey data [J].Lancet Reg Health West Pac,2024 ,43:100809.
[3]
心洁,壹图.《中国居民营养与慢性病状况报告(2020年)》国务院新闻办公室2020年12月23日新闻发布会(摘要) [J].中老年保健,2021,31(02):14-21.
[4]
Garvey WT,Mechanick JI,Brett EM,et al.American association of clinical endocrinologists and American college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity [J].Endocr Pract,2016,22(7):842-884.
[5]
Evert AB,Dennison M,Gardner CD,et al.Nutrition therapy for adults with diabetes or prediabetes:a consensus report [J].Diabetes Care,2019,42(5):731-754.
[6]
Wing RR,Lang W,Wadden TA,et al.Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes [J].Diabetes Care,2011,34(7):1481-1486.
[7]
Look AHEAD Research Group,Gregg EW,Jakicic JM,Blackburn G,et al.Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes:a post-hoc analysis of the look AHEAD randomised clinical trial [J].Lancet Diabetes Endocrinol,2016,4(11):913-921.
[8]
Hall KD,Kahan S.Maintenance of lost weight and long-term management of obesity [J].Med Clin North Am,2018,102(1):183-197.
[9]
Horn DB,Almandoz JP,Look M.What is clinically relevant weight loss for your patients and how can it be achieved? A narrative review[J].Postgrad Med,2022,134(4):359-375.
[10]
Gloy VL,Briel M,Bhatt DL,et al.Bariatric surgery versus nonsurgical treatment for obesity:a systematic review and meta-analysis of randomised controlled trials [J].BMJ,2013,125:461.
[11]
中华医学会内分泌学会.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):545-560.
[12]
Papamargaritis D,Le Roux CW.Do gut hormones contribute to weight loss and glycaemic outcomes after bariatric surgery?[J].Nutrients,2021,13(3):1-26.
[13]
Cegla J,Troke RC,Jones B,et al.Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food intake [J].Diabetes,2014,63(11):3711-3720.
[14]
Salem V,Izzi-Engbeaya C,Coello C,et al.Glucagon increases energy expenditure independently of brown adipose tissue activation in humans [J].Diabetes Obes Metab,2016,18(1):72-81.
[15]
Tan TM,Field BCT,McCullough KA,et al.Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyper-glycemia [J].Diabetes,2013,62(4):1131-1138.
[16]
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].Lancet Diabetes Endocrinol,2024,12(3):162-173.
[17]
Blüher M,Rosenstock J,Hoefler J,et al.Dose-response effects on HbA1c and bodyweight reduction of survodutide,a dual glucagon/GLP-1 receptor agonist,compared with placebo and open-label semaglutide in people with type 2 diabetes:a randomised clinical trial[J].Diabetologia,2024,67(3):470-482.
[18]
Ji LN,Jiang HW,Cheng ZF,et al.A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity[J].Nat Commun,2023,14(1):8289.
[19]
Innovent.玛仕度肽(IBI362)高剂量9 mg在中国肥胖受试者中的II期临床研究达到24周主要终点 [EB/OL].苏州:Innovent,2023.https://cn.innoventbio.com/#/news/485
[20]
Klein S,Nestor JJ,Harris MS,et al.Pemvidutide (ALT-801),a Balanced (1:1) GLP-1/Glucagon dual receptor agonist,induces rapid and marked weight loss without the need for dose titration in people with overweight/obesity[J].Diabetes,2022,71:334-OR.
[21]
Melson E,Ashraf U,Papamargaritis D,et al.What is the pipeline for future medications for obesity? [J].Int J Obes (Lond),2024,Online ahead of print.
[22]
Alba M,Yee J,Frustaci ME,et al.Efficacy and safety of glucagonlike peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus:a randomized doseranging study [J].Clin Obes,2021,11(2):e12432.
[23]
Lu SC,Chen M,Atangan L,et al.GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice and monkeys [J].Cell Rep Med,2021,2(5):100263.
[24]
Murielle M.Veniant,Shu-Chen Lu,Larissa Atangan,et al.A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings [J].Nat Merab,2024,6(2):290-303.
[25]
Coskun T,Urva S,Roell WC,et al.LY3437943,a novel triple glucagon,GIP,and GLP-1 receptor agonist for glycemic control and weight loss:from discovery to clinical proof of concept [J].Cell Metab.2022,34(9):1234-1247.
[26]
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.
[27]
Rosenstock J,Frias J,Jastreboff AM,et al.Retatrutide,a GIP,GLP-1 and glucagon receptor agonist,for people with type 2 diabetes:a randomised,double-blind,placebo and active-controlled,parallelgroup,phase 2 trial conducted in the USA [J].Lancet,2023,402(10401):529-544.
[28]
Knop FK,Aroda VR,do Vale RD,et al.OASIS 1 Investigators,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.
[29]
Aroda VR,Aberle J,Bardtrum L,et al.Efficacy and safety of oncedaily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS):a multicentre,randomised,phase 3b trial [J].Lancet,2023,402(10403):693-704.
[30]
Wilding J,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.
[31]
Davies M,Faerch L,J eppesen OK,et al.Semaglutide 2.4 mg once a week in adults with overweight or obesity,and type 2 diabetes(STEP2):a randomised,double-blind,double-dummy,placebocontrolled,phase 3 trial [J].Lancet,2021,397(10278):971-984.
[32]
Frias JP,Hsia S,Eyde S,et al.Efficacy and safety of oral orforglipron in patients with type 2 diabetes:a multicentre,randomised,doseresponse,phase 2 study [J].Lancet,2023,402(10400):472-483.
[33]
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.
[34]
Griffith DA,Edmonds DJ,Fortin JP,et al.A small-molecule oral agonist of the human glucagon-like peptide-1 receptor [J].J Med Chem,2022,65(12):8208-8226.
[35]
Saxena AR,Frias JP,Brown LS,et al.Efficacy and safety of oral small molecule glucagon-like peptide 1 receptor agonist danuglipron for glycemic control among patients with type 2 diabetes:a randomized clinical trial [J].JAMA Netw Open,2023,6(5):e2314493.
[36]
Lucacchini A.Amylin,Another important neuroendocrine hormone for the treatment of diabesity [J].Int J Mol Sci,2024,25(3):1517.
[37]
Dehestani B,Stratford NRS,le Roux CW.Amylin as a future obesity treatment [J].J Obes Metab Syndr,2021,30(4):320-325.
[38]
Frias JP,Deenadayalan S,Erichsen L,et al.Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes:a multicentre,randomised,double-blind,active-controlled,phase 2 trial [J].Lancet,2023,402(10403):720-730.
[39]
Sanyal AJ,Bedossa P,Fraessdorf M,et al.A phase 2 randomized trial of survodutide in MASH and fibrosis [J].N Engl J Med,2024,391(4):311-319.
[40]
Romero-Gómez M,Lawitz E,Shankar RR,et al.A phase IIa activecomparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease [J].J Hepatol,2023,79(4):888-897.
[41]
Innovent.信达生物玛仕度肽在减重临床III期临床研究GLORY-1中肝脏脂肪含量降幅高达80.2% [EB/OL].苏州:Innovent,2024.https://cn.innoventbio.com/#/news/564
[42]
Arun JS,Lee MK,Juan PF,et al.Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease:a randomized phase 2a trial [J].Nat Med,2024,30(7):2037-2048.
[43]
Garito T,Roubenoff R,Hompesch M,et al.Bimagrumab improves body composition and insulin sensitivity in insulin-resistant individuals [J].Diabetes Obes Metab,2018,20(1):94-102.
[44]
Heymsfield SB,Coleman LA,Miller R,et al.Effect of bimagrumab vs.placebo on body fat mass among adults with type 2 diabetes and obesity:A phase 2 randomized clinical trial [J].JAMA Netw Open,2021,4(1):e2033457.
[45]
Rooks D,Swan T,Goswami B,et al.Bimagrumab vs Optimized standard of care for treatment of sarcopenia in community-dwelling older adults:A randomized clinical trial [J].JAMA Netw Open,2020,3(10):e2020836.
[46]
Rubino D,Abrahamsson N,Davies M,et al.Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity:The STEP 4 randomized clinical trial [J].JAMA,2021,325(14):1414-1425.
[47]
Aronne LJ,Sattar N,Horn DB,et al.surmount-4 investigators,continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity:The SURMOUNT-4 randomized clinical trial [J].JAMA,2024,331(1):38-48.
[48]
Lingvay I,Agarwal S.A revolution in obesity treatment [J].Nat Med,2023,29(10):2406-2408.
[49]
Zhang L,Chen J,Zhang J,et al.Regional disparities in obesity among a heterogeneous population of Chinese children and adolescents [J].JAMA Netw Open,2021,4(10):e2131040.
[50]
Joe Eun Son.Genetics,pharmacotherapy,and dietary interventions in childhood obesity [J].J Pharm Pharm Sci,2024,27:12861.
[51]
Lingvay I,Sumithran P,le Roux CW,et al.There is no magic bullet for obesity [J].Lancet Diabetes Endocrinol,2023,11(8):541.
[52]
Verges B.Do anti-obesity medical treatment have a direct effect on adipose tissue? [J].Ann Endocrinol (Paris),2024,85(3):179-183.
[53]
Miras AD,Pérez-Pevida B,Aldhwayan M,et al.Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS):a randomised,double-blind,placebo-controlled trial [J].Lancet Diabetes Endocrinol,2019,7(7):549-559.
[1] 郝玥萦, 毛盈譞, 张羽, 汪佳旭, 韩林霖, 匡雯雯, 孟瑶, 杨秀华. 超声引导衰减参数成像评估肝脂肪变性及其对心血管疾病风险的预测价值[J/OL]. 中华医学超声杂志(电子版), 2024, 21(08): 770-777.
[2] 曹雯佳, 刘学兵, 罗安果, 钟释敏, 邓岚, 王玉琳, 李赵欢. 超声矢量血流成像对2型糖尿病患者颈动脉壁剪切应力的研究[J/OL]. 中华医学超声杂志(电子版), 2024, 21(07): 709-717.
[3] 中国医师协会外科医师分会肥胖代谢病综合管理与护理专家工作组, 中国医师协会外科医师分会肥胖和代谢病外科专家工作组, 中国肥胖代谢外科研究协作组. 肥胖代谢外科医学科普中国专家共识(2024 版)[J/OL]. 中华普通外科学文献(电子版), 2025, 19(01): 1-8.
[4] 陆嘉杰, 严帅, 蔡卫华, 吴金柱. 肥胖症患者袖状胃切除术后体重反弹的相关因素分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(03): 349-352.
[5] 赵丽霞, 王春霞, 陈一锋, 胡东平, 张维胜, 王涛, 张洪来. 内脏型肥胖对腹腔镜直肠癌根治术后早期并发症的影响[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 35-39.
[6] 孟令凯, 李大勇, 王宁, 王桂明, 张炳南, 李若彤, 潘立峰. 袖状胃切除术对肥胖伴2型糖尿病大鼠的作用及机制研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 638-642.
[7] 李猛, 姜腊, 董磊, 吴情, 贾犇黎. 腹腔镜胃袖状切除术治疗肥胖合并2型糖尿病及脂肪胰的临床研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(05): 554-557.
[8] 宋新雅, 苏小慧, 卞士柱, 丁小涵. 吸入性药物治疗肺动脉高压的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 831-835.
[9] 刘见, 杨晓波, 何均健, 吴淼. 应用电钩三孔法腹腔镜袖状胃切除术[J/OL]. 中华腔镜外科杂志(电子版), 2024, 17(06): 363-364.
[10] 冯熔熔, 苏晓乐, 王利华. 慢性肾脏病患者并发心血管疾病相关生物标志物研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(05): 273-278.
[11] 谢浩文, 丁建英, 刘小霞, 冯毅, 姚婧. 椎旁神经阻滞对微创胃切除肥胖患者术中血流、术后应激及康复质量的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 569-573.
[12] 张睿旻, 朱红梅, 刘雁军. 中国肥胖代谢外科临床研究现状及展望:一项计量学研究[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(01): 1-10.
[13] 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.
[14] 王文博, 曹耀权, 朱利勇. 新型减重药物的研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(01): 19-25.
[15] 李梦蝶, 王勇. 替西帕肽在优化减重代谢手术中的作用展望[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(01): 26-32.
阅读次数
全文


摘要