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 ›› 2024, Vol. 10 ›› Issue (02) : 88 -93. doi: 10.3877/cma.j.issn.2095-9605.2024.02.003

专家论坛

GLP-1受体激动剂——司美格鲁肽的应用及安全性
颜宥彤1, 赵锐1, 万谦益1, 张贵祥1, 沈弘毅1, 程中1, 陈亿1,()   
  1. 1. 610041 成都,四川大学华西医院胃肠外科减重外科中心
  • 收稿日期:2024-03-07 出版日期:2024-05-30
  • 通信作者: 陈亿

GLP-1 receptor agonist—application and safety of semaglutide

Youtong Yan1, Rui Zhao1, Qianyi Wan1, Guixiang Zhang1, Hongyi Shen1, Zhong Cheng1, Yi Chen1,()   

  1. 1. Bariatic Surgery Center, Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
  • Received:2024-03-07 Published:2024-05-30
  • Corresponding author: Yi Chen
引用本文:

颜宥彤, 赵锐, 万谦益, 张贵祥, 沈弘毅, 程中, 陈亿. GLP-1受体激动剂——司美格鲁肽的应用及安全性[J]. 中华肥胖与代谢病电子杂志, 2024, 10(02): 88-93.

Youtong Yan, Rui Zhao, Qianyi Wan, Guixiang Zhang, Hongyi Shen, Zhong Cheng, Yi Chen. GLP-1 receptor agonist—application and safety of semaglutide[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2024, 10(02): 88-93.

目前肥胖症治疗方法包括生活方式干预、药物治疗和减重代谢手术,但非手术策略难以使大多数患者体重持续下降。新兴的GLP-1受体激动剂(GLP-1RAs)司美格鲁肽作为一种得到证实的对肥胖症以及糖尿病等疾病具有良好治疗效果的药物,通过激活下丘脑内的GLP-1受体,调节食欲并延迟肠胃排空。但其不良反应包括低血糖、胆石症、急性胰腺炎、自伤及自杀风险增高等,现已均有报道。未来研究应进一步涵盖更多元化的人群,并开展针对中国人群的大型随机对照试验以更好地完善临床应用。本文总结了司美格鲁肽在肥胖症慢性体重管理中的作用机制、体重减轻疗效及安全性。

Current treatments for obesity include lifestyle interventions, pharmacotherapy, and bariatric metabolic surgery. However, non-surgical strategies often fail to sustain weight loss for most patients. The emerging glucagon-like peptide 1 receptor agonists (GLP-1RAs), semaglutide, has been proven effective in treating obesity and diseases such as diabetes. It works by activating GLP-1 receptors in the hypothalamus, regulating appetite, and delaying gastric emptying. However, adverse effects such as hypoglycemia, cholelithiasis, acute pancreatitis, and increased risks of self-harm and suicide have been reported. Future research should include more diverse populations and conduct large-scale randomized controlled trials targeting the Chinese population to better refine clinical applications. This review summarizes the mechanisms, weight loss efficacy, and safety of semaglutide in chronic weight management for obesity.

表1 STEP系列研究
[1]
程中, 陈亿, 颜宥彤, 等. 修正性减重手术的发展和反思 [J]. 中华消化外科杂志, 2022, 21(11): 1428-1431.
[2]
Sun X, Yan AF, Shi Z, et al. Health consequences of obesity and projected future obesity health burden in China [J]. Obesity (Silver Spring, Md.), 2022, 30(9): 1724-1751.
[3]
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.
[4]
中国营养学会肥胖防控分会, 中国营养学会临床营养分会, 中华预防医学会行为健康分会, 等. 中国居民肥胖防治专家共识 [J]. 中华流行病学杂志, 2022, 43(5): 18-26.
[5]
Jepsen MM, Christensen MB. Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity [J]. Expert Opinion on Emerging Drugs, 2021, 26(3): 231-243.
[6]
Coulman KD, Hopkins J, Brookes ST, et al. A Core outcome set for the benefits and adverse events of bariatric and metabolic surgery: The BARIACT project [J]. PLoS medicine, 2016, 13(11): e1002187.
[7]
Howick K, Griffin BT, Cryan JF, et al. From belly to brain: targeting the ghrelin receptor in appetite and food intake regulation [J]. International Journal of Molecular Sciences, 2017, 18(2): 273.
[8]
Blundell J, Finlayson G, Axelsen M, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity [J]. Diabetes, Obesity & Metabolism, 2017, 19(9): 1242-1251.
[9]
Knudsen LB, Lau J. The discovery and Development of Liraglutide and Semaglutide [J]. Frontiers in Endocrinology, 2019, 10: 155.
[10]
Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars [J]. Science (New York, N.Y.), 2005, 307(5717): 1909-1914.
[11]
Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutide lowers body weight in rodents via distributed neural pathways [J]. JCI insight, 2020, 5(6): e133429, 133429.
[12]
Campos CA, Bowen AJ, Schwartz MW, et al. Parabrachial CGRP neurons control meal termination [J]. Cell Metabolism, 2016, 23(5): 811-820.
[13]
Frank S, Veit R, Sauer H, et al. Dopamine depletion reduces food-related reward activity independent of BMI [J]. Neuropsychopharmacology, 2016, 41(6): 1551-1559.
[14]
Kadowaki T, Isendahl J, Khalid U, et al. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial [J]. The Lancet. Diabetes & Endocrinology, 2022, 10(3): 193-206.
[15]
Mu Y, Bao X, Eliaschewitz FG, et al. Efficacy and safety of once weekly semaglutide 2·4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial [J]. The Lancet. Diabetes & Endocrinology, 2024, 12(3): 184-195.
[16]
Chao AM, Tronieri JS, Amaro A, et al. Clinical insight on semaglutide for chronic weight management in adults: patient selection and special considerations [J]. Drug Design, Development and Therapy, 2022, 16: 4449-4461.
[17]
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.
[18]
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 & Metabolism, 2022, 24(8): 1553-1564.
[19]
Wharton S, Calanna S, Davies M, et al. Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss [J]. Diabetes, Obesity & Metabolism, 2022, 24(1): 94-105.
[20]
Bradley CL, McMillin SM, Hwang AY, et al. High-dose once-weekly semaglutide: a new option for obesity management [J]. The Annals of Pharmacotherapy, 2022, 56(8): 941-950.
[21]
Romera I, Cebrián-Cuenca A, álvarez-Guisasola F, et al. A review of practical issues on the use of glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes [J]. Diabetes Therapy: Research, Treatment and Education of Diabetes and Related Disorders, 2019, 10(1): 5-19.
[22]
赵翊如, 方振威, 张琳, 等. 基于FAERS数据库的成人使用司美格鲁肽的临床研究 [J]. 中国临床药理学杂志, 2024, 40(2): 264-268.
[23]
Nreu B, Dicembrini I, Tinti F, et al. Cholelithiasis in patients treated with Glucagon-Like Peptide-1 Receptor: An updated meta-analysis of randomized controlled trials [J]. Diabetes Research and Clinical Practice, 2020, 161: 108087.
[24]
Rehfeld JF, Knop FK, Asmar A, et al. Cholecystokinin secretion is suppressed by glucagon-like peptide-1: clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs [J]. Scandinavian Journal of Gastroenterology, 2018, 53(12): 1429-1432.
[25]
Smits MM, Van Raalte DH. Safety of Semaglutide [J]. Frontiers in Endocrinology, 2021, 12: 645563.
[26]
Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies [J]. Gastroenterology, 2011, 141(1): 150-156.
[27]
Giorda CB, Picariello R, Nada E, et al. Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study [J]. The Lancet. Diabetes & Endocrinology, 2014, 2(2): 111-115.
[28]
Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs—FDA and EMA assessment [J]. The New England Journal of Medicine, 2014, 370(9): 794-797.
[29]
Ji L, Dong X, Li Y, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30-week, double-blind, phase 3a, randomized trial [J]. Diabetes, Obesity & Metabolism, 2021, 23(2): 404-414.
[30]
Jeon C, Hart PA, Li L, et al. Development of a Clinical Prediction Model for Diabetes in Chronic Pancreatitis: The PREDICT3c Study [J]. Diabetes Care, 2023, 46(1): 46-55.
[31]
Bai Y, Gong G, Aierken R, et al. A retrospective study investigating the clinical significance of body mass index in acute pancreatitis [J]. PeerJ, 2024, 12: e16854.
[32]
EMA statement on ongoing review of GLP-1 receptor agonists | European Medicines Agency[EB/OL]. [2024-02-25].

URL    
[33]
Ruggiero R, Mascolo A, Spezzaferri A, et al. Glucagon-like Peptide-1 Receptor Agonists and Suicidal Ideation: Analysis of Real-Word Data Collected in the European Pharmacovigilance Database [J]. Pharmaceuticals (Basel, Switzerland), 2024, 17(2): 147.
[34]
Chen C, Zhou R, Fu F, et al. Postmarket safety profile of suicide/self-injury for GLP-1 receptor agonist: a real-world pharmacovigilance analysis [J]. European Psychiatry: The Journal of the Association of European Psychiatrists, 2023, 66(1): e99.
[35]
Zhou J, Zheng Y, Xu B, et al. Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database [J]. BMC medicine, 2024, 22(1): 65.
[36]
Wang W, Volkow ND, Berger NA, et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort [J]. Nature Medicine, 2024, 30(1): 168-176.
[37]
Khaleel MA, Khan AH, Ghadzi SMS, et al. A Standardized Dataset of a Spontaneous Adverse Event Reporting System [J]. Healthcare (Basel, Switzerland), 2022, 10(3): 420.
[38]
Able C, Liao B, Saffati G, et al. Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study [J/OL]. International Journal of Impotence Research, 2024. Online ahead of print.
[1] 聂生军, 王钰, 王毅, 鲜小庆, 马生成. 复方倍他米松局部注射联合光动力疗法治疗小型瘢痕疙瘩的临床疗效观察[J]. 中华损伤与修复杂志(电子版), 2024, 19(05): 404-410.
[2] 朴成林, 蓝炘, 司振铎, 李强, 冯健, 安峰铎, 冷建军. 胰十二指肠切除联合肝切除术疗效分析:附5例报告(附视频)[J]. 中华普通外科学文献(电子版), 2024, 18(05): 363-367.
[3] 吉顺富, 汤晓燕, 徐进. 腹腔镜近端胃癌根治术中拓展胃后间隙在肥胖患者中的应用研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 393-396.
[4] 谢丽春, 欧庆芬, 张秋萍, 叶升. 简化和标准肝脏MRI方案在结直肠癌肝转移患者随访中的临床应用[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 434-437.
[5] 莫淇舟, 苏劲, 黄健, 李健维, 李思宁, 柳建军. 智能控压输尿管软镜碎石吸引取石术在直径10~25 mm上尿路结石中的应用[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 497-502.
[6] 刘明昊, 李晨, 王冰, 万政, 田文. 机器人与腹腔镜食管裂孔疝修补术对比研究[J]. 中华疝和腹壁外科杂志(电子版), 2024, 18(04): 376-382.
[7] 韦雅丽, 范利杰. 术前右美托咪定滴鼻在腹股沟斜疝患儿腹腔镜下疝囊高位结扎术中的应用[J]. 中华疝和腹壁外科杂志(电子版), 2024, 18(04): 446-450.
[8] 黄建朋, 邹建强, 宗华. 肝移植术后腹壁疝诊治初步经验[J]. 中华疝和腹壁外科杂志(电子版), 2024, 18(04): 471-473.
[9] 杨万荣, 任治坤, 时新颍. 沙丁胺醇雾化吸入脾多肽治疗AECOPD的疗效分析[J]. 中华肺部疾病杂志(电子版), 2024, 17(04): 609-612.
[10] 梁艳娉, 列诗韵, 王艺穗, 吴晓瑛, 林颖. 基于内镜操作细节记录系统构建胃底静脉曲张内镜下组织胶注射术的标准化管理方案[J]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 705-709.
[11] 危用洋, 黄俊甫, 辛万鹏, 易思清, 涂书举, 方康, 李勇, 肖卫东. 三种术式治疗胰腺颈体部良性或低度恶性肿瘤的临床疗效分析[J]. 中华肝脏外科手术学电子杂志, 2024, 13(04): 515-519.
[12] 黄福秀, 张宁宁, 李晨阳, 李淑玲, 陈超. 单纯电切、单纯电凝与电凝电切术对扁平肠息肉疗效及不良事件发生率的影响[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 310-314.
[13] 陶金华, 陈珊珊, 陈晓四. 阿帕替尼联合替吉奥治疗晚期食管癌的疗效与安全性影响因素评价[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 325-329.
[14] 周敏, 张仁清, 卢贤红. 秋泻灵联合双歧杆菌三联活菌散对轮状病毒腹泻患儿免疫功能、心肌酶和C反应蛋白的影响[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 365-368.
[15] 袁捷, 乔钰琪, 李彦冬. 二甲双胍、来曲唑联合地屈孕酮治疗多囊卵巢综合征合并不孕症的效果评价[J]. 中华临床医师杂志(电子版), 2024, 18(04): 343-347.
阅读次数
全文


摘要