Hollander Priscilla
Ruth Collins Diabetes Center, Baylor University Medical Center at Dallas, Dallas, Texas 75246, USA.
Am J Med. 2007 Feb;120(2 Suppl 1):S18-28; discussion S29-32. doi: 10.1016/j.amjmed.2006.11.014.
Rimonabant significantly reduces weight and waist circumference and improves dyslipidemias in overweight and obese patients without diabetes mellitus. Numerous other metabolic changes, including reduced prevalence of the metabolic syndrome and associated cardiovascular disease (CVD) risk factors, reduced fasting glucose, and elevated adiponectin, have been demonstrated with the administration of rimonabant. The Rimonabant-in-Obesity (RIO)-Diabetes trial studied the safety and efficacy of rimonabant in overweight and obese patients with type 2 diabetes who were treated with metformin or sulfonylureas. RIO-Diabetes was a 1-year, randomized, double-blind, placebo-controlled, parallel-group study of 1,047 overweight/obese patients with type 2 diabetes in 151 centers in 11 countries. The body mass index of participants ranged from 27 to 40. Glycosylated hemoglobin (HbA1c) at screening ranged from 6.5% to 10.0%. All patients were receiving either metformin or sulfonylurea therapy and were asked to follow a hypocaloric diet (600 kcal/day deficit [1 kcal = 4.2 kJ]) for the duration of the trial. After a 4-week placebo plus diet run-in period, patients were randomized to receive placebo or rimonabant 5 mg or 20 mg once daily. At 1 year, absolute change in weight from baseline in the intention-to-treat, last observation carried forward analysis of the rimonabant 5 mg and 20 mg groups, respectively, was loss of 2.3 kg and 5.3 kg compared with 1.4 kg in the placebo group (P = 0.013 and P <0.001, respectively). Waist circumference was significantly decreased in the rimonabant 5-mg and 20-mg groups by 2.9 cm and 5.2 cm compared with 1.9 cm in the placebo group (P = 0.034 and P <0.001, respectively). HbA1c reductions of 0.1% and 0.6% were significant in the rimonabant 5-mg and 20-mg groups (P = 0.034 and P <0.001, respectively). Some 57% of the improvements in HbA(1c) and high-density lipoprotein cholesterol could not be attributed to observed weight loss. Compared with placebo, rimonabant 20 mg also demonstrated significant improvements in the prevalence of metabolic syndrome and improvement in its constituents, as well as systolic blood pressure and C-reactive protein levels (assay by ICON Laboratories, Farmingdale, NY and Dublin, Ireland). Rimonabant is the first selective cannabinoid1 blocker studied for type 2 diabetes and associated CVD risk factor therapy. Its ability to improve the numerous metabolic pathologies associated with diabetes and CVD risk and concomitantly to reduce weight and waist circumference introduces a strongly positive new dynamic in type 2 diabetes treatment. Its multifactorial mechanisms warrant further investigation and may provide insights into other pathologies.
利莫那班可显著降低无糖尿病的超重和肥胖患者的体重和腰围，并改善血脂异常。使用利莫那班后还出现了许多其他代谢变化，包括代谢综合征患病率及相关心血管疾病（CVD）危险因素降低、空腹血糖降低和脂联素升高。肥胖症利莫那班（RIO）-糖尿病试验研究了利莫那班在接受二甲双胍或磺脲类药物治疗的2型糖尿病超重和肥胖患者中的安全性和有效性。RIO-糖尿病试验是一项为期1年的随机、双盲、安慰剂对照、平行组研究，在11个国家的151个中心纳入了1047例2型糖尿病超重/肥胖患者。参与者的体重指数范围为27至40。筛查时糖化血红蛋白（HbA1c）范围为6.5%至10.0%。所有患者均接受二甲双胍或磺脲类药物治疗，并被要求在试验期间遵循低热量饮食（每天减少600千卡热量[1千卡=4.2千焦]）。在为期4周的安慰剂加饮食导入期后，患者被随机分配接受安慰剂或每日一次5毫克或20毫克利莫那班治疗。在1年时，在意向性治疗、末次观察结转分析中，利莫那班5毫克组和20毫克组与基线相比的体重绝对变化分别为减轻2.3千克和5.3千克，而安慰剂组为减轻1.4千克（P分别为0.013和P<0.001）。利莫那班5毫克组和20毫克组的腰围分别显著减少2.9厘米和5.2厘米，而安慰剂组减少1.9厘米（P分别为0.034和P<0.001）。利莫那班5毫克组和20毫克组的HbA1c分别显著降低0.1%和0.6%（P分别为0.034和P<0.001）。HbA1c和高密度脂蛋白胆固醇改善的约57%不能归因于观察到的体重减轻。与安慰剂相比，20毫克利莫那班还使代谢综合征患病率及其组成成分以及收缩压和C反应蛋白水平（由纽约法明代尔和爱尔兰都柏林의ICON实验室检测）有显著改善。利莫那班是首个用于2型糖尿病及相关CVD危险因素治疗研究的选择性大麻素1受体阻滞剂。其改善与糖尿病和CVD风险相关的多种代谢病变并同时减轻体重和腰围的能力为2型糖尿病治疗带来了积极的新动态。其多因素机制值得进一步研究，可能为其他病变提供见解。
