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GLP-1RA药物司美格鲁肽的临床应用研究进展
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Abstract:
司美格鲁肽作为新兴的胰高血糖素样肽-1受体激动剂(GLP-1RA)，是该药物类别中最近批准的药物，也是目前唯一可用于皮下注射和口服制剂的GLP-1RA，主要用于2型糖尿病的治疗。其药物特性可在血糖控制、胰岛素抵抗改善、体重管理、肝脏疾病上体现出显著的效果。在心脑血管疾病上也可体现出一定的治疗效果，成为当前医疗行业的热点。然而有利必有弊，司美格鲁肽的过度依赖也会伴随一些疾病的风险，如延缓胃排空导致的胃肠疾病、胰腺炎、胆道疾病等风险。本文通过分析司美格鲁肽的安全性和危险性，介绍该药物在降血糖、减重、治疗心血管疾病等多方面的进展，为临床应用提供参考。
Semaglutide, an emerging glucagon-like peptide-1 receptor agonist (GLP-1RA), is the most recently approved drug in this drug class and the only GLP-1RA currently available for subcutaneous and oral formulations, primarily for the treatment of type 2 diabetes. Its medicinal properties have been shown to be effective in blood sugar control, improvement of insulin resistance, weight management, and liver disease. It can also reflect a certain therapeutic effect in cardiovascular and cerebrovascular diseases, which has become a hot spot in the current medical industry. However, there are pros and cons, and the over-reliance on semaglutide will also be accompanied by the risk of some diseases, such as gastrointestinal diseases caused by delayed gastric emptying, pancreatitis, biliary tract diseases, etc. This article analyzes the safety and danger of semaglutide, and introduces the progress of semaglutide in blood glucose reduction, weight loss, and treatment of cardiovascular diseases, so as to provide reference for clinical application.
| [1] | Moffett, R.C., Vasu, S. and Flatt, P.R. (2015) Functional GIP Receptors Play a Major Role in Islet Compensatory Response to High Fat Feeding in Mice. Biochimica et Biophysica Acta (BBA)—General Subjects, 1850, 1206-1214. https://doi.org/10.1016/j.bbagen.2015.02.006 |
| [2] | Ahrén, B., Yamada, Y. and Seino, Y. (2021) The Mediation by GLP-1 Receptors of Glucagon-Induced Insulin Secretion Revisited in GLP-1 Receptor Knockout Mice. Peptides, 135, Article ID: 170434. https://doi.org/10.1016/j.peptides.2020.170434 |
| [3] | 洪毅颖. GLP-1RA药物司美格鲁肽的临床研究进展[J]. 中外医学研究, 2024, 22(6): 159-164. |
| [4] | 章菁仪, 焦丽君, 王欣燕. GLP-1RA对心血管疾病作用的研究进展[J]. 心血管康复医学杂志, 2024, 33(3): 364-367. |
| [5] | Shao, D., Zhao, L. and Sun, J. (2024) Synthesis and Clinical Application of Representative Small-Molecule Dipeptidyl Peptidase-4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes Mellitus (T2DM). European Journal of Medicinal Chemistry, 272, Article ID: 116464. https://doi.org/10.1016/j.ejmech.2024.116464 |
| [6] | 崔佳乐, 杨艳, 彭雅茗, 等. GLP-1RA在2型糖尿病中的应用进展[J]. 医学综述, 2021, 27(4): 778-782+787. |
| [7] | Phillips, A. and Clements, J.N. (2021) Clinical Review of Subcutaneous Semaglutide for Obesity. Journal of Clinical Pharmacy and Therapeutics, 47, 184-193. https://doi.org/10.1111/jcpt.13574 |
| [8] | Srikanth, T., Little, B.B., et al. (2019) Type 2 Diabetes Mellitus (T2DM) “Remission” in Non-Bariatric Patients 65 Years and Older. Frontiers in Public Health, 7, 82. |
| [9] | (2024) Correction to: 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. Nephrology Dialysis Transplantation, 39, 724. |
| [10] | Morgan, T.J., Scott, P.H., Anstey, C.M. and Bowling, F.G. (2020) Hyperlactatemia in Diabetic Ketoacidosis Is Common and Can Be Prolonged: Lactate Time-Series from 25 Intensive Care Admissions. Journal of Clinical Monitoring and Computing, 35, 757-764. https://doi.org/10.1007/s10877-020-00532-9 |
| [11] | García-Vega, D., Sánchez-López, D., Rodríguez-Carnero, G., Villar-Taibo, R., Viñuela, J.E., Lestegás-Soto, A., et al. (2024) Semaglutide Modulates Prothrombotic and Atherosclerotic Mechanisms, Associated with Epicardial Fat, Neutrophils and Endothelial Cells Network. Cardiovascular Diabetology, 23, Article No. 1. https://doi.org/10.1186/s12933-023-02096-9 |
| [12] | Vitale, M., Orsi, E., Solini, A., Garofolo, M., Resi, V., Bonora, E., et al. (2024) Independent Association of History of Diabetic Foot with All-Cause Mortality in Patients with Type 2 Diabetes: The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. Cardiovascular Diabetology, 23, Article No. 34. https://doi.org/10.1186/s12933-023-02107-9 |
| [13] | Giovanazzi, A., Gios, L., Mastellaro, M., Gentilini, M.A., Valent, F., Condini, S., et al. (2023) Organisational Models Supported by Technology for the Management of Diabetic Disease and Its Complications in a Diabetic Clinic Setting: Study Protocol for a Randomised Controlled Trial Targeting Type 2 Diabetes Individuals with Non-Ideal Glycaemic Values (Telemechron Study). Trials, 24, Article No. 513. https://doi.org/10.1186/s13063-023-07515-6 |
| [14] | Kashyap, S.R., Gatmaitan, P., Brethauer, S. and Schauer, P. (2010) Bariatric Surgery for Type 2 Diabetes: Weighing the Impact for Obese Patients. Cleveland Clinic Journal of Medicine, 77, 468-476. https://doi.org/10.3949/ccjm.77a.09135 |
| [15] | Chang, S., Stoll, C.R.T., Song, J., Varela, J.E., Eagon, C.J. and Colditz, G.A. (2014) The Effectiveness and Risks of Bariatric Surgery: An Updated Systematic Review and Meta-Analysis, 2003-2012. JAMA Surgery, 149, 275-287. https://doi.org/10.1001/jamasurg.2013.3654 |
| [16] | Keidar, A. (2011) Bariatric Surgery for Type 2 Diabetes Reversal: The Risks. Diabetes Care, 34, S361-S266. https://doi.org/10.2337/dc11-s254 |
| [17] | Gagnon, L.E. and Karwacki Sheff, E.J. (2012) Outcomes and Complications after Bariatric Surgery. AJN, American Journal of Nursing, 112, 26-36. https://doi.org/10.1097/01.naj.0000418920.45600.7a |
| [18] | Lingvay, I., Sumithran, P., Cohen, R.V. and le Roux, C.W. (2022) Obesity Management as a Primary Treatment Goal for Type 2 Diabetes: Time to Reframe the Conversation. The Lancet, 399, 394-405. https://doi.org/10.1016/s0140-6736(21)01919-x |
| [19] | 李婷, 孙衍, 李娜. 司美格鲁肽联合二甲双胍治疗超重2型糖尿病的临床效果[J]. 齐齐哈尔医学院学报, 2024, 45(10): 923-927. |
| [20] | Aroda, V.R., Bain, S.C., Cariou, B., Piletič, M., Rose, L., Axelsen, M., et al. (2017) Efficacy and Safety of Once-Weekly Semaglutide versus Once-Daily Insulin Glargine as Add-On to Metformin (with or without Sulfonylureas) in Insulin-Naive Patients with Type 2 Diabetes (SUSTAIN 4): A Randomised, Open-Label, Parallel-Group, Multicentre, Multinational, Phase 3a Trial. The Lancet Diabetes & Endocrinology, 5, 355-366. https://doi.org/10.1016/s2213-8587(17)30085-2 |
| [21] | 俞恬, 刘少华, 魏安华, 等. 胰高血糖素样肽1受体激动剂治疗合并超重或肥胖的2型糖尿病的疗效和安全性的Meta分析[J]. 药物流行病学杂志, 2024, 33(5): 519-538. |
| [22] | Andreadis, P., Karagiannis, T., Malandris, K., Avgerinos, I., Liakos, A., Manolopoulos, A., et al. (2018) Semaglutide for Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis. Diabetes, Obesity and Metabolism, 20, 2255-2263. https://doi.org/10.1111/dom.13361 |
| [23] | 谷卓琪, 阮贞, 沈杨. 司美格鲁肽和度拉糖肽的控制成本分析[J]. 中国医院药学杂志, 2023, 43(9): 1002-1007. |
| [24] | Knud, F. (1922) Nosography in Modern Internal Medicine. Annals of Medical History, 4, 61-63. |
| [25] | Bray, G.A., Kim, K.K. and Wilding, J.P.H. (2017) Obesity: A Chronic Relapsing Progressive Disease Process. A Position Statement of the World Obesity Federation. Obesity Reviews, 18, 715-723. https://doi.org/10.1111/obr.12551 |
| [26] | 谭莺, 雷普润, 唐齐, 等. 中国肥胖症药物治疗的现状及效果分析[J]. 中国预防医学杂志, 2024, 25(4): 413-418. |
| [27] | Jepsen, M.M. and Christensen, M.B. (2021) Emerging Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Obesity. Expert Opinion on Emerging Drugs, 26, 231-243. https://doi.org/10.1080/14728214.2021.1947240 |
| [28] | 钱童心. 司美格鲁肽在国内获批减重适应证[N]. 第一财经日报, 2024-06-26(A09). |
| [29] | 孔思美, 王畅, 王冰梅. 减肥药司美格鲁肽的临床应用与作用机制概述[J]. 生物学教学, 2024, 49(5): 2-5. |
| [30] | 柯志强, 马倩倩, 李丹, 等. GLP-1受体激动剂对心血管作用的研究进展[J]. 中国药理学通报, 2024, 40(3): 426-430. |
| [31] | Natale, F., Luisi, E., Franzese, R., Mollo, N., Solimene, A., Caso, V.M., et al. (2024) Semaglutide in Cardiometabolic Diseases: Selecting the Target Population. Journal of Cardiovascular Development and Disease, 11, Article No. 145. https://doi.org/10.3390/jcdd11050145 |
| [32] | Lee, Y.-S., Park, M., Choung, J., et al. (2012) Glucagon-Like Peptide-1 Inhibits Adipose Tissue Macrophage Infiltration and Inflammation in an Obese Mouse Model of Diabetes. Diabetologia, 55, 2456-2468. https://doi.org/10.1007/s00125-012-2592-3 |
| [33] | Giulia, B., Laura, M., Elena, M.L., et al. (2022) The Anti-Inflammatory and Immunological Properties of GLP-1 Receptor Agonists. Pharmacological Research, 182, Article ID: 106320. |
| [34] | Rubino, D.M., Greenway, F.L., Khalid, U., O’Neil, P.M., Rosenstock, J., Sørrig, R., et al. (2022) Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults with Overweight or Obesity without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA, 327, 138-150. https://doi.org/10.1001/jama.2021.23619 |
| [35] | Amaro, A., Skolnik, N.S. and Sugimoto, D. (2022) Cardiometabolic Risk Factors Efficacy of Semaglutide in the STEP Program. Postgraduate Medicine, 134, 18-27. https://doi.org/10.1080/00325481.2022.2147325 |
| [36] | Weghuber, D., Barrett, T., Barrientos-Pérez, M., Gies, I., Hesse, D., Jeppesen, O.K., et al. (2022) Once-Weekly Semaglutide in Adolescents with Obesity. New England Journal of Medicine, 387, 2245-2257. https://doi.org/10.1056/nejmoa2208601 |
| [37] | Eslam, M., Sanyal, A.J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., et al. (2020) MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology, 158, 1999-2014.e1. https://doi.org/10.1053/j.gastro.2019.11.312 |
| [38] | Godoy-Matos, A.F., Silva Júnior, W.S. and Valerio, C.M. (2020) NAFLD as a Continuum: From Obesity to Metabolic Syndrome and Diabetes. Diabetology & Metabolic Syndrome, 12, Article No. 60. https://doi.org/10.1186/s13098-020-00570-y |
| [39] | Koureta, E. and Cholongitas, E. (2024) Evolving Role of Semaglutide in NAFLD: In Combination, Weekly and Oral Administration. Frontiers in Pharmacology, 15, Article ID: 1343587. https://doi.org/10.3389/fphar.2024.1343587 |
| [40] | Loomba, R., Abdelmalek, M.F., Armstrong, M.J., Jara, M., Kjær, M.S., Krarup, N., et al. (2023) Semaglutide 2.4 mg Once Weekly in Patients with Non-Alcoholic Steatohepatitis-Related Cirrhosis: A Randomised, Placebo-Controlled Phase 2 Trial. The Lancet Gastroenterology & Hepatology, 8, 511-522. https://doi.org/10.1016/s2468-1253(23)00068-7 |
| [41] | Chen, L. (2024) Semaglutide Alleviates Early Brain Injury Following Subarachnoid Hemorrhage by Suppressing Ferroptosis and Neuroinflammation via SIRT1 Pathway. American Journal of Translational Research, 16, 1102-1117. https://doi.org/10.62347/izgj1332 |
| [42] | Wharton, S., Calanna, S., Davies, M., Dicker, D., Goldman, B., Lingvay, I., et al. (2021) 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. Diabetes, Obesity and Metabolism, 24, 94-105. https://doi.org/10.1111/dom.14551 |
| [43] | Tobaiqy, M. and Elkout, H. (2024) Psychiatric Adverse Events Associated with Semaglutide, Liraglutide and Tirzepatide: A Pharmacovigilance Analysis of Individual Case Safety Reports Submitted to the Eudravigilance Database. International Journal of Clinical Pharmacy, 46, 488-495. https://doi.org/10.1007/s11096-023-01694-7 |
| [44] | Carpenter, K.M., Hasin, D.S., Allison, D.B. and Faith, M.S. (2000) Relationships between Obesity and DSM-IV Major Depressive Disorder, Suicide Ideation, and Suicide Attempts: Results from a General Population Study. American Journal of Public Health, 90, 251-257. |
| [45] | Roux, L.W.C., Astrup, A., Fujioka, K., et al. (2017) 3 Years of Liraglutide versus Placebo for Type 2 Diabetes Risk Reduction and Weight Management in Individuals with Prediabetes: A Randomised, Double-Blind Trial. The Lancet, 389, 1399-1409. |
| [46] | Smits, M.M. and Van Raalte, D.H. (2021) Safety of Semaglutide. Frontiers in Endocrinology, 12, Article ID: 645563. |
