胰淀素
胰淀素是由胰岛Beta细胞分泌的抑制食欲的肽,可以辅助胰岛素控制血糖水平。 它也可以减少胃排空,可以在肥胖患者中恢复瘦素的敏感性。 在与饮食、运动和行为治疗联合使用时,普兰林肽(胰淀素的合成类似物)可增加肥胖患者 12 个月的减重效果。[179]Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care. 2008 Sep;31(9):1816-23.http://care.diabetesjournals.org/content/31/9/1816.longhttp://www.ncbi.nlm.nih.gov/pubmed/18753666?tool=bestpractice.com[180]Dunican KC, Adams NM, Desilets AR. The role of pramlintide for weight loss. Ann Pharmacother. 2010 Mar;44(3):538-45.http://www.ncbi.nlm.nih.gov/pubmed/20164472?tool=bestpractice.com
内源性大麻素拮抗剂
大麻受体CB1的拮抗剂有抑制食欲的作用。 数种 CB1 受体阻滞剂正在进行临床试验。[181]Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet. 2007 Jan 6;369(9555):71-7.http://www.ncbi.nlm.nih.gov/pubmed/17208644?tool=bestpractice.com[182]Aronne LJ, Tonstad S, Moreno M, et al. A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist, in obese and overweight patients: a high-dose study. Int J Obes (Lond). 2010 May;34(5):919-35.http://www.ncbi.nlm.nih.gov/pubmed/20157323?tool=bestpractice.com[183]Kipnes MS, Hollander P, Fujioka K, et al. A one-year study to assess the safety and efficacy of the CB1R inverse agonist taranabant in overweight and obese patients with type 2 diabetes. Diabetes Obes Metab. 2010 Jun;12(6):517-31.http://onlinelibrary.wiley.com/doi/10.1111/j.1463-1326.2009.01188.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20518807?tool=bestpractice.com[184]Proietto J, Rissanen A, Harp JB, et al. A clinical trial assessing the safety and efficacy of the CB1R inverse agonist taranabant in obese and overweight patients: low-dose study. Int J Obes (Lond). 2010 Aug;34(8):1243-54.http://www.ncbi.nlm.nih.gov/pubmed/20212496?tool=bestpractice.com 利莫那班减少腹内脂肪,在一项随机对照研究中能改善多种心血管代谢风险因素,但被发现和自杀率增加相关。[185]Després JP, Ross R, Boka G, et al; ADAGIO-Lipids Investigators. Effect of rimonabant on the high-triglyceride/ low-HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat: the ADAGIO-Lipids trial. Arterioscler Thromb Vasc Biol. 2009 Mar;29(3):416-23.http://atvb.ahajournals.org/cgi/content/full/29/3/416http://www.ncbi.nlm.nih.gov/pubmed/19112166?tool=bestpractice.com[186]Chavez-Tapia NC, Tellez-Avila FI, Bedogni G, et al. Systematic review and meta-analysis on the adverse events of rimonabant treatment: considerations for its potential use in hepatology. BMC Gastroenterol. 2009 Oct 9;9:75.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763866/http://www.ncbi.nlm.nih.gov/pubmed/19818116?tool=bestpractice.com[187]Topol EJ, Bousser MG, Fox KA, et al. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. Lancet. 2010 Aug 14;376(9740):517-23.http://www.ncbi.nlm.nih.gov/pubmed/20709233?tool=bestpractice.com
肠促胰素
肠促胰素促进胰岛分泌胰岛素,减慢胃排空,减少胰高糖素分泌。 Exendin-4是一种内源性肠促胰素,也是胰高血糖素样肽-1(GLP-1)受体的激动剂,有降糖的作用,也对中枢神经系统有潜在的抑制食欲的作用。 艾塞那肽(合成的Exendin-4)已获准治疗2型糖尿病患者,在临床试验中应用于肥胖的治疗。 3 年临床试验的结果显示,在糖尿病肥胖患者中,艾塞那肽有利于减重和改善血糖控制。[188]Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008 Jan;24(1):275-86.http://www.ncbi.nlm.nih.gov/pubmed/18053320?tool=bestpractice.com[189]Bradley DP, Kulstad R, Schoeller DA. Exenatide and weight loss. Nutrition. 2010 Mar;26(3):243-9.http://www.ncbi.nlm.nih.gov/pubmed/20152707?tool=bestpractice.com
葛瑞林
对这种饥饿激素的拮抗研究仍处于临床前阶段。[37]Holst B, Schwartz TW. Constitutive ghrelin receptor activity as a signaling set-point in appetite regulation. Trends Pharmacol Sci. 2004 Mar;25(3):113-7.http://www.ncbi.nlm.nih.gov/pubmed/15058279?tool=bestpractice.com
儿茶素
应用绿茶儿茶酚或者应用表没食子儿茶素(epigallocatechin)及咖啡因和BMI、体重、腰围下降有关。 但是,这种减少的临床意义最多为中度。[190]Phung OJ, Baker WL, Matthews LJ, et al. Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis. Am J Clin Nutr. 2010 Jan;91(1):73-81.http://ajcn.nutrition.org/content/91/1/73.longhttp://www.ncbi.nlm.nih.gov/pubmed/19906797?tool=bestpractice.com[191]Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysis. Int J Obes (Lond). 2009 Sep;33(9):956-61.http://www.ncbi.nlm.nih.gov/pubmed/19597519?tool=bestpractice.com
人生长激素(hGH)
外源性hGH可以抑制脂蛋白脂肪酶、减少脂肪细胞的体积,但也可以造成高糖。 人生长激素(hGH)肽的抑制脂蛋白脂肪酶的区域曾被分离下来,但这个片段似乎并不会引起糖尿病。 一项 meta 分析显示,重组生长激素治疗可减轻内脏肥胖,无总体减重效果。[192]Mekala KC, Tritos NA. Effects of recombinant human growth hormone therapy in obesity in adults: a meta analysis. J Clin Endocrinol Metab. 2009 Jan;94(1):130-7.http://jcem.endojournals.org/cgi/content/full/94/1/130http://www.ncbi.nlm.nih.gov/pubmed/18940879?tool=bestpractice.com 其他发现包括对血清脂质的积极影响,但伴有血浆葡萄糖升高。[192]Mekala KC, Tritos NA. Effects of recombinant human growth hormone therapy in obesity in adults: a meta analysis. J Clin Endocrinol Metab. 2009 Jan;94(1):130-7.http://jcem.endojournals.org/cgi/content/full/94/1/130http://www.ncbi.nlm.nih.gov/pubmed/18940879?tool=bestpractice.com
甲状腺激素
发现甲状腺激素的应用在肥胖患者卡路里受限时减轻体重,能改善成人非甲状腺病态综合征的发病率和死亡率。 但是对于治疗肥胖和非甲状腺病态综合征中应用甲状腺激素的疗效的数据结果并不统一。 数据支持此治疗可引发亚临床甲亢。[193]Kaptein EM, Beale E, Chan LS. Thyroid hormone therapy for obesity and nonthyroidal illnesses: a systematic review. J Clin Endocrinol Metab. 2009 Oct;94(10):3663-75.http://www.ncbi.nlm.nih.gov/pubmed/19737920?tool=bestpractice.com
脂肪酶抑制剂
另一个脂肪酶抑制剂,称为ATL-962尚在临床试验中。 这个药物似乎较奥利司他的严重不良反应少。
二甲双胍
小型临床试验显示,二甲双胍可作为降低体重的辅助药物,对甘油三酯和血浆葡萄糖均有积极的影响。[194]Desilets AR, Dhakal-Karki S, Dunican KC. Role of metformin for weight management in patients without type 2 diabetes. Ann Pharmacother. 2008 Jun;42(6):817-26.http://www.ncbi.nlm.nih.gov/pubmed/18477733?tool=bestpractice.com 尚需大规模临床试验。
胃泌酸调节素
胃泌酸调节素是一种抑制食欲的肽,包含胰高糖素序列,胃泌酸调节素由肠道进食后分泌, 目前临床试验正在进行中。
胰多肽(PP)
胰多肽是一种抑制食欲的肽,进食后由胰腺和肠道远端释放。 人工合成的胰多肽类似物现在正在临床试验中。
5-羟色胺-去甲肾上腺素再摄取抑制剂及5-羟色胺激动剂
已知 5-羟色胺再摄取抑制有厌食的作用(例如西布曲明)。[181]Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet. 2007 Jan 6;369(9555):71-7.http://www.ncbi.nlm.nih.gov/pubmed/17208644?tool=bestpractice.com 特索芬辛是一种去甲肾上腺素、多巴胺和 5-羟色胺再摄取抑制剂,已在一项 II 期试验中证实特索芬辛作为饮食辅助干预手段的有效性。[195]Astrup A, Madsbad S, Breum L, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Nov 29;372(9653):1906-13.http://www.ncbi.nlm.nih.gov/pubmed/18950853?tool=bestpractice.com 多个选择性5-羟色胺激动剂正在临床试验中。
胰高糖素样肽受体激动剂
除了对收缩压、舒张压、胆固醇和血糖控制的有益作用外,胰高血糖素样多肽受体激动剂还可能实现减重。[196]Vilsbøll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012 Jan 10;344:d7771.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256253/http://www.ncbi.nlm.nih.gov/pubmed/22236411?tool=bestpractice.com
迷走神经阻滞
美国食品药品监督管理局已批准可逆性间歇迷走神经阻滞装置,例如 Maestro Rechargeable System,用于治疗肥胖症。[197]Ikramuddin S, Blackstone RP, Brancatisano A, et al. Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial. JAMA. 2014 Sep 3;312(9):915-22.http://jama.jamanetwork.com/article.aspx?articleid=1900511http://www.ncbi.nlm.nih.gov/pubmed/25182100?tool=bestpractice.com 迷走神经阻滞已被证实可引发饱腹感,从而实现减重和血糖控制。[198]Shikora S, Toouli J, Herrera MF, et al. Vagal blocking improves glycemic control and elevated blood pressure in obese subjects with type 2 diabetes mellitus. J Obes. 2013;2013:245683.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745954/http://www.ncbi.nlm.nih.gov/pubmed/23984050?tool=bestpractice.com[199]Sarr MG, Billington CJ, Brancatisano R, et al. The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity. Obes Surg. 2012 Nov;22(11):1771-82.http://www.ncbi.nlm.nih.gov/pubmed/22956251?tool=bestpractice.com
十二指肠-空肠旁路衬垫
十二指肠-空肠旁路衬垫是一种不可渗透的套管,经内镜植入至近端肠道,以在食物和肠壁之间形成屏障。 一项随机临床试验显示,在肥胖和 2 型糖尿病患者中,十二指肠-空肠旁路衬垫联合饮食相比单用饮食能更有效地减轻体重。[200]Koehestanie P, de Jonge C, Berends FJ, et al. The effect of the endoscopic duodenal-jejunal bypass liner on obesity and type 2 diabetes mellitus, a multicenter randomized controlled trial. Ann Surg. 2014 Dec;260(6):984-92.http://www.ncbi.nlm.nih.gov/pubmed/25072436?tool=bestpractice.com