胰高血糖素样肽-1受体激动剂的临床应用及围术期研究进展

doi:10.3969/j.issn.1006-7795.2024.06.024

摘要/Abstract

摘要： 胰高血糖素样肽-1受体激动剂（glucagon like peptide-1 receptor agonists，GLP-1RA）在控制2型糖尿病（type 2 diabetes mellitus，T2DM）患者的血糖水平及减轻肥胖患者体质量方面具有重要治疗地位。通过作用于分布于全身的GLP-1R，该药对人体其他重要系统也可产生一定影响,如可减少心血管事件发生率、延缓慢性肾脏病进展、增加消化系统不良事件发生风险等。随着该药物使用人群的不断增加，患者可能出现胃排空延迟、返流及误吸等围术期不良事件，需引起临床重视。本文针对该类药物的药理学特点及其围术期相关研究综述如下。

关键词: 胰高血糖素样肽-1受体激动剂, 围术期, 2型糖尿病, 减肥药

Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have an important therapeutic role in controlling blood glucose levels in patients with type 2 diabetes mellitus (T2DM) and reducing body weight in obese patients. Recent studies have showed that by acting on GLP-1R distributed throughout the body, the drug may also have some effect on other important systems of the body, such as reducing the incidence of cardiovascular events, delaying the progression of chronic kidney disease, and increasing the risk of adverse events in the digestive system. As the use of this drug increase in the population, the potential for patients to experience an increase in perioperative adverse events such as delayed gastric emptying and the occurrence of reflux aspiration needs to be emphasized. This article summarizes the pharmacological characteristics of these drugs and their perioperative studies as follows.

Key words: glucagon-like peptide-1 receptor agonists, perioperative period, type 2 diabetes mellitus, diet pills

中图分类号:

R969.3

王恬园, 于芸, 韩如泉. 胰高血糖素样肽-1受体激动剂的临床应用及围术期研究进展[J]. 首都医科大学学报, 2024, 45(6): 1115-1121.

Wang Tianyuan, Yu Yun, Han Ruquan. Advances in clinical application and perioperative studies of glucagon-like peptide-1 receptor agonists[J]. Journal of Capital Medical University, 2024, 45(6): 1115-1121.

参考文献

［1］蒋镜清, 符玲, 谈梦璐, 等. 胰高血糖素样肽-1(GLP-1)类似物研究进展［J］. 高校化学工程学报, 2020, 34(6): 1327－1338.
［2］ Tasyurek H M, Altunbas H A, Balci M K, et al. Incretins: their physiology and application in the treatment of diabetes mellitus［J］. Diabetes Metab Res Rev, 2014, 30(5): 354－371.
［3］ Das A, Geetha K M, Hazarika I. Contemporary updates on the physiology of glucagon like peptide-1 and its agonist to treat type 2 diabetes mellitus［J］. Int J Pept Res Ther, 2020, 26(3): 1211－1221.
［4］ Hussein H, Zaccardi F, Khunti K, et al. Efficacy and tolerability of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis［J］. Diabetes Obes Metab, 2020, 22(7): 1035－1046.
［5］ Smits M M, Van raalte D H.Safety of semaglutide［J］. Front Endocrinol,2021,12:645563.
［6］ Xie Z Y, Yang S S, Deng W S, et al. Efficacy and safety of liraglutide and semaglutide on weight loss in people with obesity or overweight: a systematic review［J］. Clin Epidemiol, 2022, 14: 1463－1476.
［7］ Trujillo J. Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes［J］. J Clin Pharm Ther, 2020, 45 Suppl 1(Suppl 1): 43－60.
［8］ American Diabetes Association Professional Practice Committee. 16. Diabetes care in the hospital: standards of care in diabetes-2024［J］. Diabetes Care, 2024, 47(Suppl 1): S295－S306.
［9］ Grunvald E, Shah R, Hernaez R, et al. AGA clinical practice guideline on pharmacological interventions for adults with obesity［J］. Gastroenterology, 2022, 163(5): 1198－1225.
［10］ Wu F, Smith M R, Mueller A L, et al. Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: a historical cohort study［J］. Can J Anaesth, 2024, 71(7): 958－966.
［11］ Wu T X, Zhang Y, Shi Y F, et al. Safety of glucagon-like peptide-1 receptor agonists: a real-world study based on the US FDA adverse event reporting system database［J］. Clin Drug Investig, 2022, 42(11): 965－975.
［12］ Garvey W T, Batterham R L, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial［J］. Nat Med, 2022, 28(10): 2083－2091.
［13］ Sodhi M, Rezaeianzadeh R, Kezouh A, et al. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss［J］. JAMA, 2023, 330(18): 1795－1797.
［14］ Gruen D S, Guyette F X, Brown J B, et al. Association of prehospital plasma with survival in patients with traumatic brain injury: a secondary analysis of the PAMPer cluster randomized clinical trial［J］. JAMA Netw Open, 2020, 3(10): e2016869.
［15］ Husain M, Birkenfeld A L, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes［J］. N Engl J Med, 2019, 381(9): 841－851.
［16］ Marso S P, Bain S C, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes［J］. N Engl J Med, 2016, 375(19): 1834－1844.
［17］ Ryan D H, Lingvay I, Colhoun H M, et al. Semaglutide effects on cardiovascular outcomes in people with overweight or obesity (SELECT) rationale and design ［J］. Am Heart J, 2020, 229: 61－69.
［18］ Lincoff A M, Brown-Frandsen K, Colhoun H M, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes［J］. N Engl J Med, 2023, 389(24): 2221－2232.
［19］ McGuire D K, Busui R P, Deanfield J, et al. Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial［J］. Diabetes Obes Metab, 2023, 25(7): 1932－1941.
［20］ Nauck M A, Quast D R. Cardiovascular safety and benefits of semaglutide in patients with type 2 diabetes: findings from SUSTAIN 6 and PIONEER 6［J］. Front Endocrinol, 2021, 12: 645566.
［21］ Shaman A M, Bain S C, Bakris G L, et al. Effect of the glucagon-like peptide-1 receptor agonists semaglutide and liraglutide on kidney outcomes in patients with type 2 diabetes: pooled analysis of SUSTAIN 6 and LEADER［J］. Circulation, 2022, 145(8): 575－585.
［22］ Rossing P, Baeres F M M, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease［J］. Nephrol Dial Transplant, 2023, 38(9): 2041－2051.
［23］ Perkovic V, Tuttle K R, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes［J］. N Engl J Med, 2024, 391(2): 109－121.
［24］ Kuhre R E, Deacon C F, Holst J J, et al. What is an L-cell and how do we study the secretory mechanisms of the L-cell?［J］. Front Endocrinol, 2021, 12: 694284.
［25］ Botfield H F, Uldall M S, Westgate C S J, et al. A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydrocephalus［J］. Sci Transl Med, 2017, 9(404): eaan0972.
［26］ Hulst A, Visscher M, Godfried M, et al. Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients-A multicentre, prospective, randomised superiority trial［J］. J Cardiothorac Vasc Anesth, 2019, 33, Supplement 2: S89.
［27］纪立农. 胰高糖素样肽-1受体激动剂改善代谢综合征的临床应用研究进展［J］. 中华糖尿病杂志, 2023, 15(12): 1177－1184.
［28］ Sherwin M, Hamburger J, Katz D, et al. Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: a prospective observational study in volunteers without obesity recently started on semaglutide［J］. Can J Anaesth, 2023, 70(8): 1300－1306.
［29］ Silveira S Q, da Silva L M, de Campos Vieira Abib A, et al. Relationship between perioperative semaglutide use and residual gastric content: A retrospective analysis of patients undergoing elective upper endoscopy［J］. J Clin Anesth, 2023, 87: 111091.
［30］ Joshi G P. Anesthetic considerations in adult patients on glucagon-like peptide-1 receptor agonists: gastrointestinal focus［J］. Anesth Analg, 2024, 138(1): 216－220.
［31］ Klein S R, Hobai I A. Semaglutide, delayed gastric emptying, and intraoperative pulmonary aspiration: a case report［J］. Can J Anaesth, 2023, 70(8): 1394－1396.
［32］ Gulak M A, Murphy P. Regurgitation under anesthesia in a fasted patient prescribed semaglutide for weight loss: a case report［J］. Can J Anaesth, 2023, 70(8): 1397－1400.
［33］ van Bloemendaal L, IJzerman R G, Ten Kulve J S, et al. GLP-1 receptor activation modulates appetite-and reward-related brain areas in humans［J］. Diabetes, 2014, 63(12): 4186－4196.
［34］ Jones P M, Hobai I A, Murphy P M. Anesthesia and glucagon-like peptide-1 receptor agonists: proceed with caution!［J］. Can J Anaesth, 2023, 70(8): 1281－1286.
［35］ Kindel T L, Wang A Y, Wadhwa A, et al. Multisociety clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period ［J］. Clin Gastroenterol Hepatol, 2024.10.1016/j.cgh.2024.10.003
［36］ Jensen L, Kupcova V, Arold G, et al. Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment［J］. Diabetes Obes Metab, 2018, 20(4): 998－1005.
［37］ Yabut J M, Drucker D J. Glucagon-like peptide-1 receptor-based therapeutics for metabolic liver disease［J］. Endocr Rev, 2023, 44(1): 14－32.
［38］ Li S L, Wang Z M, Xu C, et al. Liraglutide attenuates hepatic ischemia-reperfusion injury by modulating macrophage polarization［J］. Front Immunol, 2022, 13: 869050.
［39］ Yang C T, Yao W Y, Yang C Y, et al. Lower risks of cirrhosis and hepatocellular carcinoma with GLP-1RAs in type 2 diabetes: a nationwide cohort study using target trial emulation framework［J］. J Intern Med, 2024, 295(3): 357－368.
［40］ Zhao X, Huang K, Zheng M J, et al. Effect of liraglutide on blood pressure: a meta-analysis of liraglutide randomized controlled trials［J］. BMC Endocr Disord, 2019, 19(1): 4.
［41］ Sokos G G, Nikolaidis L A, Mankad S, et al. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure［J］. J Card Fail, 2006, 12(9): 694－699.
［42］ Hulst A H, Visscher M J, Cherpanath T G V, et al. Effects of liraglutide on myocardial function after cardiac surgery: a secondary analysis of the randomised controlled GLOBE trial［J］. J Clin Med, 2020, 9(3): 673.
［43］ Virani S S, Newby L K, Arnold S V, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American heart association/American college of cardiology joint committee on clinical practice guidelines［J］. Circulation, 2023, 148(9): e9－e119.
［44］ Gerstein H C, Colhoun H M, Dagenais G R, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial［J］. Lancet, 2019, 394(10193): 121－130.
［45］ Mitchell J L, Lyons H S, Walker J K, et al. The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial［J］. Brain, 2023, 146(5): 1821－1830.

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