Sjöström L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar H P, Krempf M
Sahlgrenska University Hospital, Göteborg, Sweden.
Lancet. 1998 Jul 18;352(9123):167-72. doi: 10.1016/s0140-6736(97)11509-4.
We undertook a randomised controlled trial to assess the efficacy and tolerability of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period.
743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet.
From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p<0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p<0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p<0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments.
Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.
我们进行了一项随机对照试验，以评估胃肠道脂肪酶抑制剂奥利司他在两年时间里促进肥胖患者体重减轻及防止体重反弹的疗效和耐受性。
在15个欧洲中心招募的743名患者（体重指数28 - 47kg/m²）进入为期4周的单盲、安慰剂导入期，采用轻度低热量饮食（每天热量 deficit 600千卡）。完成导入期的688名患者被随机分配接受120mg奥利司他（每日三次）或安慰剂的双盲治疗，为期1年，并配合低热量饮食。在第二个为期52周的双盲期，患者改用维持体重（热量平衡）饮食，并重新分配接受奥利司他或安慰剂治疗。
从导入期开始到第1年末，奥利司他组平均体重减轻比安慰剂组更多（10.2%[10.3kg]对6.1%[6.1kg]；从随机分组到第1年末的LSM差异为3.9kg[p<0.001]）。在第2年，继续使用奥利司他的患者平均体重反弹量仅为改用安慰剂患者的一半（p<0.001）。从安慰剂改用奥利司他的患者在第2年额外减重0.9kg，而继续使用安慰剂的患者平均反弹2.5kg（p<0.001）。奥利司他组的总胆固醇、低密度脂蛋白（LDL）胆固醇、LDL/高密度脂蛋白比值以及血糖和胰岛素浓度的下降幅度均大于安慰剂组。胃肠道不良事件在奥利司他组更为常见。两种治疗期间其他不良症状的发生频率相似。
在两年时间里，奥利司他配合适当饮食可促进肥胖患者实现具有临床意义的体重减轻并减少体重反弹。超过两年使用奥利司他需要在疗效和不良事件方面进行仔细监测。
