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穆峰达® (替尔泊肽注射液)
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在 1 期试验中,与安慰剂相比,替尔泊肽通过减少 2 型糖尿病(T2D)成人患者的脂肪量、食欲和能量摄入,以及减少无 T2D 的肥胖成人患者的食物摄入量、食欲和对食物的渴望来减轻体重。
减重的作用机制
在一项针对 T2D 成人患者的 1 期研究中,与安慰剂和司美格鲁肽 1 mg 相比,使用替尔泊肽 15 mg 治疗的患者 28 周后体重显著下降。其主要原因是
- 脂肪量减少,以及
- 食欲和能量摄入减少。1
在这项研究中,
在另一项针对未患 T2D 的肥胖成人的 1 期研究中,与安慰剂相比,使用替尔泊肽 15 mg 治疗的患者 18 周后体重显著下降。3
在这项研究中,与安慰剂相比,使用替尔泊肽 15 mg 治疗对代谢适应没有影响,但显示出每日脂肪氧化量显著增加。3
此外,从基线到第 18 周,与安慰剂相比,替尔泊肽 15 mg
- 减少了随意午餐和晚餐的食物摄入量
- 降低了食欲,以及
- 降低了对食物的渴望程度。4
与通过限制热量摄入来减轻体重的安慰剂相比,替尔泊肽并未影响以下指标的下降
- 睡眠代谢率,或
- 24 小时久坐的能量消耗。3
替尔泊肽诱导的体重减轻不受以下因素影响:
胃肠道不良事件和延缓胃排空不太可能是替尔泊肽减轻体重的机制。介导分析表明,胃肠道不良事件对替尔泊肽减轻体重的影响始终极小。替尔泊肽可延缓胃排空,但效果是短暂的,并且重复给药会产生快速抗药反应。因此,这不太可能是替尔泊肽持续减轻体重的机制。5,6
GIP 和 GLP-1 在减轻体重中的作用
GIP 和 GLP-1 是食物摄入和食欲的生理调节剂,在临床前研究中发现它们位于大脑中对食欲调节非常重要的区域。7-9
临床前和临床数据表明,GIP 有助于调节脂肪组织中的脂质代谢。7-13
上次审阅日期:2025年11月17日
参考文献
1. Heise T, DeVries JH, Urva S, et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with type 2 diabetes. Diabetes Care. 2023;46(5):998-1004. https://doi.org/10.2337/dc22-1710
2. Heise T, DeVries JH, Urva S, et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with T2D. Abstract presented at: American Diabetes Association; June 3-7, 2022; New Orleans, United States.
3. Ravussin E, Sanchez-Delgado G, Martin CK, et al. The effect of tirzepatide during weight loss on metabolic adaptation, fat oxidation and food intake in people with obesity. Abstract presented at: 83rd Scientific Session of the American Diabetes Association; June 23-26, 2023; San Diego, CA, USA.
4. Martin CK, Ravussin E, Sanchez-Delgado G, et al. The effect of tirzepatide during weight loss on food intake, appetite, food preference and food craving in people with obesity. Abstract presented at: 83rd Scientific Session of the American Diabetes Association; June 23-26, 2023; San Diego, CA, USA
5. Rubino DM, Pedersen SD, Connery L, et al. Tolerability and weight reduction of tirzepatide in adults with obesity or overweight. Poster presented at: Obesity Week; October 14-17; Dallas, TX.
6. Urva S, Coskun T, Loghin C, et al. The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1 receptor agonists. Diabetes Obes Metab. 2020;22(10):1886-1891. https://doi.org/10.1111/dom.14110
7. Adriaenssens AE, Gribble FM, Reimann F, The glucose-dependent insulinotropic polypeptide signaling axis in the central nervous system. Peptides. 2020:125;70194. https://doi.org/10.1016/j.peptides.2019.170194
8. Zhang Q, Delessa CT, Augustin R, et al. The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling. Cell Metabol. 2021:33(4):833-844.e5. https://doi.org/10.1016/j.cmet.2021.01.015
9. Adriaenssens AE, Biggs EK, Darwish T, et al. Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 2019;30(5):987-996.e6. https://doi.org/10.1016/j.cmet.2019.07.013
10. Kim SJ, Nian C, Karunakaran S, et al. GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. PLoS One. 2012:7(7):e40156. https://doi.org/10.1371/journal.pone.0040156
11. Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab. 2018;18:3-14. www.doi.org/10.1016/j.molmet.2018.09.009
12. Geisler CE, Antonellis MP, Trumbauer WM, et al. Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents. Diabetes Obes Metab. 2023;25(1):56-67. https://doi.org/10.1111/dom.14843
13. Costa A, Ai M, Nunn N, et al. Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation. Mol Metab. 2022;55:101407. https://doi.org/10.1016/j.molmet.2021.101407
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