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Pharmacy Information 2026
新型减重药物临床应用研究进展
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Abstract:
肥胖已成为全球性公共卫生问题,易诱发糖尿病、心脑血管疾病等多种并发症,严重威胁百姓身体健康。单纯依靠饮食管控与运动锻炼进行减重,患者长期依从性较差,整体干预效果有限,减重药物现已成为肥胖综合诊疗中重要的辅助治疗手段。当前临床常用减重药物主要分为脂肪酶抑制剂、GLP-1受体激动剂及中枢复方制剂三大类,主流用药包含奥利司他、利拉鲁肽、司美格鲁肽、贝那鲁肽、奥氟格列隆、替尔泊肽、玛仕度肽、瑞他鲁肽、纳曲酮/安非他酮、芬特明/托吡酯等。本文归纳各类减重药物的作用机理、临床疗效及安全特性,分析现阶段药物应用存在的实际问题,探讨减重药物研发方向与临床应用发展趋势,为临床科学选用减重药物、规范开展肥胖药物治疗提供参考依据。
Obesity has evolved into a global public health crisis, as it predisposes individuals to multiple complications such as diabetes mellitus and cardiovascular and cerebrovascular diseases, thereby posing a severe threat to human health. Weight management relying solely on dietary restriction and physical exercise often suffers from poor long-term patient adherence and limited overall intervention efficacy. Consequently, anti-obesity medications have become an essential adjunctive therapy in the comprehensive diagnosis and treatment of obesity. Clinically prevalent anti-obesity drugs are primarily categorized into three classes: lipase inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and central nervous system combination preparations. The mainstream agents include orlistat, liraglutide, semaglutide, benaglutide, orforglipron, tirzepatide, mazdutide, retatrutide, naltrexone/bupropion, and phentermine/topiramate. This article systematically summarizes the mechanisms of action, clinical efficacy and safety profiles of each class of anti-obesity drugs, analyzes the practical challenges associated with their current clinical application, and discusses the research priorities and developmental trends of anti-obesity drugs. It aims to provide evidence-based references for rational medication selection and standardized pharmacotherapy for obesity in clinical practice.
| [1] | Pan, X.F., Fang, Z.Z., Zhang, L.L. and Pan, A. (2025) Obesity in China: Current Progress and Future Prospects. The Lancet Diabetes & Endocrinology, 14, 178-186. https://doi.org/10.1016/s2213-8587(25)00357-2 |
| [2] | Wang, Z., Du, W.W., Wei, X.Q., Li, S., Zhang, J.G., Ju, L.H., et al. (2026) Clinical Obesity among Chinese Adults: Prevalence, Multimorbidity Burden, and Associations with Physical Activity. Nutrients, 18, 983-998. https://doi.org/10.3390/nu18060983 |
| [3] | Rubino, F., Cummings, D.E., Eckel, R.H., Cohen, R.V., Wilding, J.P.H., Brown, W.A., et al. (2025) Definition and Diagnostic Criteria of Clinical Obesity. The Lancet Diabetes & Endocrinology, 13, 221-262. https://doi.org/10.1016/s2213-8587(24)00316-4 |
| [4] | The Lancet Diabetes & Endocrinology (2025) Redefining Obesity: Advancing Care for Better Lives. The Lancet Diabetes & Endocrinology, 13, Article 75. https://doi.org/10.1016/s2213-8587(25)00004-x |
| [5] | Varady, K.A., Cienfuegos, S., Ezpeleta, M. and Gabel, K. (2022) Clinical Application of Intermittent Fasting for Weight Loss: Progress and Future Directions. Nature Reviews Endocrinology, 18, 309-321. https://doi.org/10.1038/s41574-022-00638-x |
| [6] | Chao, A.M., Quigley, K.M. and Wadden, T.A. (2021) Dietary Interventions for Obesity: Clinical and Mechanistic Findings. Journal of Clinical Investigation, 131, 1-10. https://doi.org/10.1172/jci140065 |
| [7] | Moon, J. and Koh, G. (2020) Clinical Evidence and Mechanisms of High-Protein Diet-Induced Weight Loss. Journal of Obesity & Metabolic Syndrome, 29, 166-173. https://doi.org/10.7570/jomes20028 |
| [8] | Heck, A.M., Yanovski, J.A. and Calis, K.A. (2000) Orlistat, a New Lipase Inhibitor for the Management of Obesity. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 20, 270-279. https://doi.org/10.1592/phco.20.4.270.34882 |
| [9] | Shi, Q.Y., Wang, Y., Hao, Q.K., Vandvik, P.O., Guyatt, G., Li, J., et al. (2024) Pharmacotherapy for Adults with Overweight and Obesity: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials. Lancet, 403, e21-e31. https://doi.org/10.1016/S0140-6736(24)00351-9 |
| [10] | Smith, S.R., Stenlof, K.S., Greenway, F.L., McHutchison, J., Schwartz, S.M., Dev, V.B., et al. (2011) Orlistat 60 Mg Reduces Visceral Adipose Tissue: A 24‐Week Randomized, Placebo‐Controlled, Multicenter Trial. Obesity, 19, 1796-1803. https://doi.org/10.1038/oby.2011.143 |
| [11] | Henness, S. and Perry, C.M. (2006) Orlistat: A Review of Its Use in the Management of Obesity. Drugs, 66, 1625-1656. https://doi.org/10.2165/00003495-200666120-00012 |
| [12] | Lupianez‐Merly, C., Dilmaghani, S., Vosoughi, K. and Camilleri, M. (2024) Review Article: Pharmacologic Management of Obesity-Updates on Approved Medications, Indications and Risks. Alimentary Pharmacology & Therapeutics, 59, 475-491. https://doi.org/10.1111/apt.17856 |
| [13] | 国家食品药品监督管理局. 关于修订奥利司他制剂说明书的通知[EB/OL]. http://www.nmpa.gov.cn/directory/web/nmpa/xxgk/ggtg/ypggtg/ypshmshxdgg/20100901161901610.html, 2010-09-01. |
| [14] | Bode, B. (2011) Liraglutide: A Review of the First Once-Daily GLP-1 Receptor Agonist. American Journal of Managed Care, 17, S59-S70. |
| [15] | Astrup, A., Carraro, R., Finer, N., Harper, A., Kunesova, M., Lean, M.E.J., et al. (2011) Safety, Tolerability and Sustained Weight Loss over 2 Years with the Once-Daily Human GLP-1 Analog, Liraglutide. International Journal of Obesity, 36, 843-854. https://doi.org/10.1038/ijo.2011.158 |
| [16] | Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., et al. (2015) A Randomized, Controlled Trial of 3.0 Mg of Liraglutide in Weight Management. New England Journal of Medicine, 373, 11-22. https://doi.org/10.1056/nejmoa1411892 |
| [17] | Lundgren, J.R., Janus, C., Jensen, S.B.K., Juhl, C.R., Olsen, L.M., Christensen, R.M., et al. (2021) Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. New England Journal of Medicine, 384, 1719-1730. https://doi.org/10.1056/nejmoa2028198 |
| [18] | Ishihara, Y., Nishiguchi, S., Branch, J. and Tanaka, E. (2022) Suspected Gastroparesis with Concurrent Gastroesophageal Reflux Disease Induced by Low-Dose Liraglutide. Cureus, 14, 1-4. https://doi.org/10.7759/cureus.26916 |
| [19] | 何明, 程俊铭, 张源, 等. GLP-1RA 类药物在减重治疗中的临床应用效果[J]. 中华肥胖与代谢病电子杂志, 2022, 8(4): 225-230. |
| [20] | Wilding, J.P.H., Batterham, R.L., Calanna, S., Davies, M., Van Gaal, L.F., Lingvay, I., et al. (2021) Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384, 989-1002. https://doi.org/10.1056/nejmoa2032183 |
| [21] | Davies, M., Færch, L., Jeppesen, O.K., Pakseresht, A., Pedersen, S.D., Perreault, L., et al. (2021) Semaglutide 2·4 Mg Once a Week in Adults with Overweight or Obesity, and Type 2 Diabetes (STEP 2): A Randomised, Double-Blind, Double-Dummy, Placebo-Controlled, Phase 3 Trial. The Lancet, 397, 971-984. https://doi.org/10.1016/s0140-6736(21)00213-0 |
| [22] | 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. JAMA, 327, 138-150. https://doi.org/10.1001/jama.2021.23619 |
| [23] | Domenica, R., Niclas, A., Melanie, D., Dan, H., Frank, L.G., Camilla, J., et al. (2021) Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults with Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA, 324, 1414-1425. |
| [24] | Garvey, W.T., Batterham, R.L., Bhatta, M., Buscemi, S., Christensen, L.N., Frias, J.P., et al. (2022) Two-Year Effects of Semaglutide in Adults with Overweight or Obesity: The STEP 5 Trial. Nature Medicine, 28, 2083-2091. https://doi.org/10.1038/s41591-022-02026-4 |
| [25] | 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 |
| [26] | Lin, P.P., Li, C.Q., Liu, Y.P., Sun, F.F., Hsieh, T., Zhang, L., et al. (2024) Pharmacokinetics and Safety Profiles of Beinaglutide Injection, a Recombinant Human GLP-1, in Adults with Overweight/Obesity: Results from a Phase I Clinical Trial. Frontiers in Pharmacology, 15, Article ID: 1433587. https://doi.org/10.3389/fphar.2024.1433587 |
| [27] | Smits, M.M., Tonneijck, L., Muskiet, M.H.A., Kramer, M.H.H., Cahen, D.L. and van Raalte, D.H. (2016) Gastrointestinal Actions of Glucagon‐Like Peptide‐1‐Based Therapies: Glycaemic Control Beyond the Pancreas. Diabetes, Obesity and Metabolism, 18, 224-235. https://doi.org/10.1111/dom.12593 |
| [28] | 方晨, 许岚, 刘煜, 等. 贝那鲁肽每日2次注射治疗中国肥胖症患者的前瞻性多中心临床研究[J]. 中华糖尿病杂志, 2024, 16(6): 663-668. |
| [29] | Kawai, T., Sun, B., Yoshino, H., Feng, D., Suzuki, Y., Fukazawa, M., et al. (2020) Structural Basis for GLP-1 Receptor Activation by LY3502970, an Orally Active Nonpeptide Agonist. Proceedings of the National Academy of Sciences, 117, 29959-29967. https://doi.org/10.1073/pnas.2014879117 |
| [30] | Food and Drug Administration (2025) FDA Direct: FDA Awards Six National Priority Vouchers. https://www.fda.gov/news-events/fda-direct-podcast/fda-direct-fda-awards-six-national-priority-vouchers |
| [31] | 国家药品监督管理局药品审评中心. 受理品种目录[DB/OL]. https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d, 2026-01-10. |
| [32] | Eli Lilly and Company (2026) FDA Approves Lilly’s Foundayo™ (Orforglipron), the only GLP-1 Pill for Weight Loss that Can be Taken any Time of Day without Food or Water Restrictions. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-foundayotm-orforglipron-only-glp-1-pill |
| [33] | Frias, J.P., Hsia, S., Eyde, S., Liu, R., Ma, X., Konig, M., et al. (2023) Efficacy and Safety of Oral Orforglipron in Patients with Type 2 Diabetes: A Multicentre, Randomised, Dose-Response, Phase 2 Study. The Lancet, 402, 472-483. https://doi.org/10.1016/s0140-6736(23)01302-8 |
| [34] | Aronne, L.J., Horn, D.B., le Roux, C.W., Chao, A.M., Ho, W., Halpern, B., et al. (2026) Orforglipron for Maintenance of Body Weight Reduction: The Double-Blind, Randomized Phase 3b ATTAIN-MAINTAIN Trial. Nature Medicine. https://doi.org/10.1038/s41591-026-04386-7 |
| [35] | Forzano, I., Varzideh, F., Avvisato, R., Jankauskas, S.S., Mone, P. and Santulli, G. (2022) Tirzepatide: A Systematic Update. International Journal of Molecular Sciences, 23, Article 14631. https://doi.org/10.3390/ijms232314631 |
| [36] | Jastreboff, A.M., Aronne, L.J., Ahmad, N.N., Wharton, S., Connery, L., Alves, B., et al. (2022) Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 387, 205-216. https://doi.org/10.1056/nejmoa2206038 |
| [37] | Wadden, T.A., Chao, A.M., Machineni, S., Kushner, R., Ard, J., Srivastava, G., et al. (2023) Tirzepatide after Intensive Lifestyle Intervention in Adults with Overweight or Obesity: The SURMOUNT-3 Phase 3 Trial. Nature Medicine, 29, 2909-2918. https://doi.org/10.1038/s41591-023-02597-w |
| [38] | Aronne, L.J., Sattar, N., Horn, D.B., Bays, H.E., Wharton, S., Lin, W., et al. (2024) Continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA, 331, 38-48. https://doi.org/10.1001/jama.2023.24945 |
| [39] | Zhao, L., Cheng, Z., Lu, Y., Liu, M., Chen, H., Zhang, M., et al. (2024) Tirzepatide for Weight Reduction in Chinese Adults with Obesity. JAMA, 332, E1-E10. https://doi.org/10.1001/jama.2024.9217 |
| [40] | Gudzune, K.A. and Kushner, R.F. (2024) Medications for Obesity: A Review. JAMA, 332, 571-584. https://doi.org/10.1001/jama.2024.10816 |
| [41] | Aronne, L.J., Horn, D.B., le Roux, C.W., Ho, W., Falcon, B.L., Gomez Valderas, E., et al. (2025) Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. New England Journal of Medicine, 393, 26-36. https://doi.org/10.1056/nejmoa2416394 |
| [42] | 国家药品监督管理局. 国家药监局批准玛仕度肽注射液上市[EB/OL]. https://www.nmpa.gov.cn/zhuanti/cxylqx/cxypxx/20250627145044169.html, 2025-06-27. |
| [43] | Ji, L.N., Jiang, H.W., Bi, Y., Li, H., Tian, J., Liu, D., et al. (2025) Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. New England Journal of Medicine, 392, 2215-2225. https://doi.org/10.1056/nejmoa2411528 |
| [44] | Shirley, M. (2025) Mazdutide: First Approval. Drugs, 85, 1621-1627. https://doi.org/10.1007/s40265-025-02249-y |
| [45] | 蔡晓凌, 陈莉明, 郭立新, 等. 胰高血糖素/胰高血糖素样肽⁃1双受体激动剂玛仕度肽临床应用专家指导意见[J].中华糖尿病杂志, 2025, 33(12): 881-887. |
| [46] | Eli Lilly and Company (2026) Lilly’s Triple agonist, Retatrutide, Delivered Powerful Weight Loss in Pivotal Phase 3 Obesity Trial. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss |
| [47] | Onakpoya, I.J., Lee, J.J., Mahtani, K.R., Aronson, J.K. and Heneghan, C.J. (2020) Naltrexone-Bupropion (Mysimba) in Management of Obesity: A Systematic Review and Meta‐Analysis of Unpublished Clinical Study Reports. British Journal of Clinical Pharmacology, 86, 646-667. https://doi.org/10.1111/bcp.14210 |
| [48] | Elmaleh-Sachs, A., Schwartz, J.L., Bramante, C.T., Nicklas, J.M., Gudzune, K.A. and Jay, M. (2023) Obesity Management in Adults. JAMA, 330, 2000-2015. https://doi.org/10.1001/jama.2023.19897 |
| [49] | U.S. Food and Drug Administration (2022) FDA Approves Treatment for Chronic Weight Management in Pediatric Patients Aged 12 Years and Older. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-chronic-weight-management-pediatric-patients-aged-12-years-and-older?f_link_type=f_linkinlinenote&flow_extra=eyJkb2NfaWQiOiI1YWU3ZmM4M |
| [50] | Allison, D.B., Gadde, K.M., Garvey, W.T., Peterson, C.A., Schwiers, M.L., Najarian, T., et al. (2012) Controlled‐Release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial (Equip). Obesity, 20, 330-342. https://doi.org/10.1038/oby.2011.330 |
| [51] | U. S. Food and Drug Administration (2012) Qsymia (Phentermine Hydrochloride; Topiramate) [Prescribing Information]. |
| [52] | Marso, S.P., Bain, S.C., Consoli, A., Eliaschewitz, F.G., Jódar, E., Leiter, L.A., et al. (2016) Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 375, 1834-1844. https://doi.org/10.1056/nejmoa1607141 |
| [53] | Dahlberg, S., Chang, E.T., Weiss, S.R., Dopart, P., Gould, E. and Ritchey, M.E. (2022) Use of Contrave, Naltrexone with Bupropion, Bupropion, or Naltrexone and Major Adverse Cardiovascular Events: A Systematic Literature Review. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 15, 3049-3067. https://doi.org/10.2147/dmso.s381652 |