针对经选择患者组全部患者的治疗推荐
第一选择
奥利司他
:
每天3次,每次120mg口服,与含脂肪食物同餐进食,最多服用4年
第二选择
或
利拉鲁肽
:
起始剂量 0.6 mg,皮下注射,每日一次,根据反应每周增加剂量,最大为 3 mg/日
或
纳曲酮/盐酸丁胺苯丙酮
:
8 mg(纳曲酮)/90 mg(丁胺苯丙酮),口服(缓释型),每日一次(早上),连续 1 周,之后 8/90 mg,每日两次,连续 1 周,之后早上 16/180 mg,晚上 8/90 mg,连续 1 周,之后 16/180 mg,每日两次。
或
盐酸芬特明/托吡酯
:
起始剂量 3.75 mg(芬特明)/23 mg(托吡酯)(缓释型),口服,每日一次(早上),连续 14 天,之后根据反应逐渐增量,最大剂量为 15 mg(芬特明)/92 mg(托吡酯)/天
更多
盐酸芬特明/托吡酯
如到第 12 周初始减重不到 3%,应停药。
第三选择
苯丁胺
:
每天1次,每次15到37.5mg,最多4周
添加药物是饮食和运动的辅助干预手段之一。[1]Jensen MD, Ryan DH, Apovian CM, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014 Jun 24;129(25 suppl 2):S102-38.http://circ.ahajournals.org/content/129/25_suppl_2/S102.longhttp://www.ncbi.nlm.nih.gov/pubmed/24222017?tool=bestpractice.com
大多数肥胖药物的问题是因其不良反应导致依从性差和用药中断。
另外,大部分肥胖药物并不作为长期治疗的推荐。
奥利司他是脂肪吸收的抑制剂(抑制胃及胰脂肪酶)。 研究已证实,奥利司他在仅联合饮食和运动时有中度疗效(减重大约 5%),但常见轻度胃肠道副作用。 [
]In people with hypertension, what are the long-term effects of orlistat?https://cochranelibrary.com/cca/doi/10.1002/cca.1352/full显示答案 联合奥利司他和左旋肉碱可以较单用奥利司他提供更好的疗效。[141]Derosa G, Maffioli P, Ferrari I, et al. Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Endocr J. 2010;57(9):777-86.https://www.jstage.jst.go.jp/article/endocrj/57/9/57_K10E-049/_pdfhttp://www.ncbi.nlm.nih.gov/pubmed/20683173?tool=bestpractice.com 之前推荐西布曲明;但是因临床试验数据显示心脏病发作和卒中的风险增加,生产商于 2010 年 10 月将其主动从美国市场撤市。[155]James WP, Caterson ID, Coutinho W, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010 Sep 2;363(10):905-17.http://www.nejm.org/doi/full/10.1056/NEJMoa1003114#t=articleTophttp://www.ncbi.nlm.nih.gov/pubmed/20818901?tool=bestpractice.com 美国食品药品监督管理局 (FDA) 已经建议患者停止使用此药,并就替代治疗咨询他们的医生。 虽然以前在欧洲建议使用西布曲明,但欧洲药品管理局 (EMA) 在 2010 年 1 月出于安全考虑暂停了西布曲明在欧盟地区的销售许可。[156]European Medicines Agency. Press release: European Medicines Agency recommends suspension of marketing authorisations for sibutramine. January 2010. http://www.ema.europa.eu/ (last accessed 12 September 2016).http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2010/01/WC500069995.pdf
氯卡色林是一种选择性 5-HT 2C 受体激动剂,在与生活方式调整计划联合使用时,可实现中度的剂量依赖性减重(5% 至 10%)。[143]Munoz-Rivas N. A randomized, multicentric trial on lorcaserin versus placebo in the management of overweight and obesity. Revista Clinica Espanola. 2011;211:52-53.[142]Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011 Oct;96(10):3067-77.http://www.ncbi.nlm.nih.gov/pubmed/21795446?tool=bestpractice.com
芬特明是一种苯丙胺/食欲抑制剂,在很多国家并不推荐。
FDA 已批准两种口服联合治疗与生活方式调整联合用于长期体重管理:一种包含芬特明和托吡酯(一种抗惊厥药),[144]Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Apr 16;377(9774):1341-52.http://www.ncbi.nlm.nih.gov/pubmed/21481449?tool=bestpractice.com[145]Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012 Feb;20(2):330-42.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270297/http://www.ncbi.nlm.nih.gov/pubmed/22051941?tool=bestpractice.com[146]Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012 Feb;95(2):297-308.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260065/http://www.ncbi.nlm.nih.gov/pubmed/22158731?tool=bestpractice.com 另一种含有纳曲酮(一种阿片受体拮抗剂)和安非他酮(一种去甲肾上腺素-多巴胺再摄取抑制剂)。[147]Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595-605.http://www.ncbi.nlm.nih.gov/pubmed/20673995?tool=bestpractice.com[148]Greenway FL, Dunayevich E, Tollefson G, et al. Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo. J Clin Endocrinol Metab. 2009 Dec;94(12):4898-906.http://www.ncbi.nlm.nih.gov/pubmed/19846734?tool=bestpractice.com[149]Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013 May;21(5):935-43.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739931/http://www.ncbi.nlm.nih.gov/pubmed/23408728?tool=bestpractice.com[150]Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011 Jan;19(1):110-20.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459776/http://www.ncbi.nlm.nih.gov/pubmed/20559296?tool=bestpractice.com[151]Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013 Dec;36(12):4022-9.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836105/http://www.ncbi.nlm.nih.gov/pubmed/24144653?tool=bestpractice.com 纳曲酮/丁胺苯丙酮也在欧洲获准用于肥胖或超重成人的体重管理。芬特明/托吡酯未在欧洲获得批准,基于安全性考虑,已拒绝批准此药。芬特明/托吡酯会增加唇腭裂的风险,因此不应用于怀孕女性。
高剂量利拉鲁肽(一种皮下注射给药的胰高血糖素样多肽-1 受体激动剂)也已在欧洲和美国获准作为体育活动和低卡路里饮食的辅助干预手段,用于管理肥胖或超重成人的体重。[152]Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA. 2015 Aug 18;314(7):687-99.http://www.ncbi.nlm.nih.gov/pubmed/26284720?tool=bestpractice.com[153]Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015 Jul 2;373(1):11-22.http://www.nejm.org/doi/full/10.1056/NEJMoa1411892#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/26132939?tool=bestpractice.com 利拉鲁肽的随机对照试验已被作为“饱腹感和临床肥胖-非糖尿病和糖尿病个体中的利拉鲁肽证据 (SCALE)”项目的一部分而实施。[154]Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013 Nov;37(11):1443-51.http://www.ncbi.nlm.nih.gov/pubmed/23812094?tool=bestpractice.com