Aronne L J
Cornell University Medical College, New York, NY 10021, USA.
J Am Diet Assoc. 1998 Oct;98(10 Suppl 2):S23-6. doi: 10.1016/s0002-8223(98)00706-8.
The medical model of obesity treatment--combining diet, exercise, and behavior modification with antiobesity agents--suffered a setback when fenfluramine and dexfenfluramine were withdrawn from the market because of an association between these medications and valvular regurgitation. The Food and Drug Administration has recently approved sibutramine (Meridia), a norepinephrine and serotonin reuptake inhibitor that was originally developed as an antidepressant, but which has also been shown to reduce weight. In a 1-year placebo-controlled trial, 65% of patients receiving 15 mg sibutramine daily lost more than 5% of their body weight, compared with 29% of patients receiving a placebo; 39% of patients in the sibutramine group lost more than 10% of their body weight, compared with 8% of patients in the placebo group. Health benefits observed in patients receiving sibutramine include reductions in levels of triglycerides, uric acid, total cholesterol, and low-density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL) cholesterol levels. Another antiobesity drug currently under review by the Food and Drug Administration is orlistat (Xenical), a pancreatic lipase inhibitor that reduces the absorption of dietary fat by approximately 30%, thus reducing energy intake. In a 1-year placebo-controlled trial, 55% of patients receiving orlistat lost more than 5% of their body weight, and 25% lost more than 10% of their body weight, compared with 33% and 15%, respectively, of patients in the placebo group. In addition, orlistat slowed the rate of weight regain in the second year of treatment. Health benefits demonstrated in clinical trials of orlistat include reduced LDL cholesterol levels and increased levels of HDL cholesterol, reduced blood pressure and fasting insulin levels, improved oral glucose tolerance test outcomes, and improved glycemic control in obese patients with diabetes. The future of the pharmacologic treatment of obesity is promising. Many new antiobesity agents are in the early stages of development, and our understanding of the body's weight-regulating mechanisms is advancing steadily. Human trials of recombinant leptin are underway. Other promising compounds include those that block the Neuropeptide Y5 and Y1 (NY5, NY1) and Melanocortin-4 (MC4) receptors, stimulate uncoupling proteins, and unbind corticotrophin-releasing factor from its binding protein. As better medical treatments for obesity become available, the focus in dietary prescription may shift away from reducing energy intake toward healthier eating for disease prevention. At present, a comprehensive approach, which, in some patients, may include medical therapy as an adjunct, is necessary to treat obesity effectively.
肥胖治疗的医学模式——将饮食、运动、行为矫正与抗肥胖药物相结合——在芬氟拉明和右芬氟拉明因与瓣膜反流有关联而退出市场时遭遇了挫折。美国食品药品监督管理局最近批准了西布曲明（诺美亭），这是一种去甲肾上腺素和5-羟色胺再摄取抑制剂，最初是作为抗抑郁药开发的，但也已被证明能减轻体重。在一项为期1年的安慰剂对照试验中，每日服用15毫克西布曲明的患者中有65%体重减轻超过5%，而服用安慰剂的患者中这一比例为29%；西布曲明组中有39%的患者体重减轻超过10%，而安慰剂组中这一比例为8%。服用西布曲明的患者所观察到的健康益处包括甘油三酯、尿酸、总胆固醇和低密度脂蛋白（LDL）胆固醇水平降低，以及高密度脂蛋白（HDL）胆固醇水平升高。美国食品药品监督管理局目前正在审评的另一种抗肥胖药物是奥利司他（赛尼可），它是一种胰脂肪酶抑制剂，可使膳食脂肪的吸收减少约30%，从而减少能量摄入。在一项为期1年的安慰剂对照试验中，服用奥利司他的患者中有55%体重减轻超过5%，25%体重减轻超过10%，而安慰剂组患者的这两个比例分别为33%和15%。此外，奥利司他减缓了治疗第二年体重反弹的速度。奥利司他临床试验所证明的健康益处包括LDL胆固醇水平降低、HDL胆固醇水平升高、血压和空腹胰岛素水平降低、口服葡萄糖耐量试验结果改善，以及肥胖糖尿病患者的血糖控制得到改善。肥胖药物治疗的前景很广阔。许多新型抗肥胖药物正处于研发的早期阶段，而且我们对人体体重调节机制的认识正在稳步推进。重组瘦素的人体试验正在进行中。其他有前景的化合物包括那些能阻断神经肽Y5和Y1（NY5、NY1）以及黑皮质素-4（MC4）受体、刺激解偶联蛋白，以及使促肾上腺皮质激素释放因子与其结合蛋白解离的化合物。随着更好的肥胖医学治疗方法问世，饮食处方的重点可能会从减少能量摄入转向为预防疾病而进行更健康的饮食。目前，对于有效治疗肥胖而言，采取综合方法是必要的，在某些患者中，这可能包括将药物治疗作为辅助手段。
