Drent M L, Larsson I, William-Olsson T, Quaade F, Czubayko F, von Bergmann K, Strobel W, Sjöström L, van der Veen E A
Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
Int J Obes Relat Metab Disord. 1995 Apr;19(4):221-6.
To evaluate efficacy and tolerability of the lipase inhibitor Orlistat (Ro 18-0647) in doses of 10, 60 and 120 mg three times a day in addition to a mild hypocaloric diet containing 30% of calories as fat.
4 week single-blind placebo run-in period of diet alone followed by a 12 week double-blind, placebo-controlled, randomized treatment period.
Five European outpatient clinics specializing in endocrinology and/or the treatment of obesity, one central laboratory.
Of 237 healthy obese subjects meeting the inclusion criteria, 188 showed compliance to the diet during the run-in period and were randomized for the treatment period.
Primary efficacy criterion was the difference in weight loss after 12 weeks of treatment between the Orlistat treated groups and the diet alone group. Secondary efficacy criteria were changes in serum total, HDL- and LDL-cholesterol.
Compared to placebo a mean (+/- s.e.) additional weight loss of 0.63 +/- 0.54 kg with 30 mg a day (P = 0.246), 0.71 +/- 0.55 kg with 180 mg a day (P = 0.190) and 1.75 +/- 0.54 kg with 360 mg a day was seen (P = 0.001) or Orlistat was observed. Overall data indicated dose-dependency. Small decreases were seen in total and LDL-cholesterol (significant in the 180 and 360 mg a day groups) and LDL- to HDL-cholesterol ratio (significant in the 360 mg a day group only). Mild, mostly gastrointestinal side effects were observed more frequently in the Orlistat groups and caused premature withdrawal from the study in only four patients. No marked laboratory abnormalities were shown, including the lipid-soluble vitamins A, D and E.
Orlistat, in an apparently dose-dependent manner, leads to additional weight loss compared to diet alone and overall, is well tolerated.
评估脂肪酶抑制剂奥利司他（Ro 18 - 0647）在每日三次服用10毫克、60毫克和120毫克剂量时，联合低热量饮食（脂肪提供30%的热量）的疗效和耐受性。
先进行为期4周的仅饮食单盲安慰剂导入期，随后是为期12周的双盲、安慰剂对照、随机治疗期。
五家欧洲专门从事内分泌学和/或肥胖症治疗的门诊诊所，一个中央实验室。
237名符合纳入标准的健康肥胖受试者中，188名在导入期遵守饮食规定，并被随机分配进入治疗期。
主要疗效标准是奥利司他治疗组与仅饮食组在治疗12周后的体重减轻差异。次要疗效标准是血清总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇的变化。
与安慰剂相比，奥利司他每日30毫克组平均（±标准误）额外体重减轻0.63±0.54千克（P = 0.246），每日180毫克组为0.71±0.55千克（P = 0.190），每日360毫克组为1.75±0.54千克（P = 0.001）。总体数据显示出剂量依赖性。总胆固醇和低密度脂蛋白胆固醇有小幅下降（在每日180毫克和360毫克组显著），低密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值仅在每日360毫克组显著下降。奥利司他组更频繁地观察到轻度的、主要是胃肠道的副作用，仅4名患者因副作用提前退出研究。未显示明显的实验室异常，包括脂溶性维生素A、D和E。
奥利司他与单纯饮食相比，以明显的剂量依赖性方式导致额外体重减轻，总体耐受性良好。
