Efficacy and Safety of Rimonabant for Improvement of Multiple Cardiometabolic Risk Factors in Overweight/Obese Patients
Efficacy and Safety of Rimonabant for Improvement of Multiple Cardiometabolic Risk Factors in Overweight/Obese Patients
复制标题
利莫那班改善超重/肥胖患者多种心脏代谢危险因素的疗效和安全性
DOI：
10.2337/dc08-s258
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发表时间：
2008
期刊：
影响因子：
16.2
通讯作者：
A. Scheen
中科院分区：
文献类型：
--
作者：
L. V. Van Gaal;X. Pi;J. Despres;C. McCarthy;A. Scheen
为了更好地确定利莫那班的疗效和安全性，第一种选择性大麻素1型（CB 1）受体拮抗剂，在大量超重和肥胖患者中使用来自三项III期非糖尿病利莫那班治疗肥胖和相关代谢疾病（RIO）研究的汇总疗效数据，来自RIO糖尿病研究的选定疗效数据，以及所有四项RIO研究的汇总安全性数据。研究设计和方法-RIO研究招募了超重（BMI >27 kg/m2）且至少有一种合并症（即，高血压、血脂异常，或对于RIO-糖尿病，2型糖尿病）或肥胖。所有患者均接受利莫那班（5或20 mg）或安慰剂每日治疗1年，外加低热量饮食（600 kcal/天不足）和增加体力活动的建议。RIO-欧洲（n = 1，508）、RIO-北美（n = 3，045）和RIO-脂质（n = 1，036）排除了2型糖尿病患者;未经治疗的血脂异常是RIO-脂质的入组要求。RIO-糖尿病（n = 1，047）要求存在磺脲类或二甲双胍单药治疗控制不佳的2型糖尿病。汇总的意向治疗人群包括5，580名非糖尿病患者（3，165名完成治疗）和1，047名糖尿病患者（692名完成治疗）。大多数疗效指标在4周的安慰剂导入期内得到改善，除了HDL胆固醇在低热量饮食的早期阶段如预期的那样下降。随机治疗1年后，非糖尿病人群中20 mg利莫那班较基线的变化如下：体重−6.5 kg，腰围−6.4 cm，HDL胆固醇+16.4%，甘油三酯− 6.9%，空腹胰岛素−0.6 μU/ml，胰岛素抵抗稳态模型评估（HOMA-IR）−0.2（与安慰剂相比，所有P均< 0.001）。在糖尿病人群中，20 mg利莫那班使A1 C水平降低0.6%（与安慰剂相比，P < 0.001）。通过ANCOVA对1年时HDL胆固醇、甘油三酯、脂联素（在RIO-脂质中）和A1 C（在RIO-糖尿病中）相对于体重的变化进行回归分析，结果表明，45-57%的利莫那班效应不能用观察到的体重减轻来解释。1年时，利莫那班更常报告的不良事件是胃肠道、神经系统和精神疾病。严重不良事件很少发生，几乎与安慰剂相当。治疗组间的总体停药率相似，但因不良事件停药除外，20 mg利莫那班与安慰剂相比发生率更高（最常见的是抑郁障碍[1.9 vs. 0.8%]、恶心[1.4 vs. 0.1%]、情绪改变伴抑郁症状[1.0 vs. 0.6%]和焦虑[1.0 vs. 0.3%]）。对精神和神经系统不良事件进行了全面审查。结论：在超重/肥胖患者中，20 mg/天的利莫那班可使体重减轻，并显著改善多种心脏代谢危险因素，如腰围、A1 C、HDL胆固醇和甘油三酯。利莫那班一般耐受良好，更常见的不良事件是胃肠道，神经和精神的性质。
OBJECTIVE—To better define the efficacy and safety of rimonabant, the first selective cannabinoid type 1 (CB1) receptor antagonist, in a large population of overweight and obese patients using pooled efficacy data from three Phase III nondiabetes Rimonabant in Obesity and Related Metabolic Disorders (RIO) studies, selected efficacy data from the RIO-Diabetes study, and pooled safety data for all four RIO studies. RESEARCH DESIGN AND METHODS—The RIO studies enrolled patients who were either overweight (BMI >27 kg/m2) with at least one comorbidity (i.e., hypertension, dyslipidemia, or, for RIO-Diabetes, type 2 diabetes) or obese. All patients received daily treatment with rimonabant (5 or 20 mg) or placebo for 1 year plus a hypocaloric diet (600 kcal/day deficit) and advice on increased physical activity. RIO-Europe (n = 1,508), RIO-North America (n = 3,045), and RIO-Lipids (n = 1,036) excluded patients with type 2 diabetes; untreated dyslipidemia was an entry requirement for RIO-Lipids. RIO-Diabetes (n = 1,047) required the presence of type 2 diabetes inadequately controlled by sulfonylurea or metformin monotherapy. RESULTS—The pooled intention-to-treat population comprised 5,580 patients without diabetes (3,165 completed treatment) and 1,047 patients with diabetes (692 completed treatment). Most efficacy measures improved during the 4-week placebo run-in period, except that HDL cholesterol decreased as expected in the early phase of a hypocaloric diet. After 1 year of randomized treatment, changes from baseline with 20 mg rimonabant in the nondiabetic population were as follows: body weight −6.5 kg, waist circumference −6.4 cm, HDL cholesterol +16.4%, triglycerides −6.9%, fasting insulin −0.6 μU/ml, and homeostasis model assessment for insulin resistance (HOMA-IR) −0.2 (all P < 0.001 vs. placebo). In the diabetic population, 20 mg rimonabant reduced A1C levels by 0.6% (P < 0.001 vs. placebo). Regression analysis of change in HDL cholesterol, triglycerides, adiponectin (in RIO-Lipids), and A1C (in RIO-Diabetes) versus body weight at 1 year by ANCOVA suggested that 45–57% of the effect of rimonabant could not be explained by the observed weight loss. At 1 year, adverse events more frequently reported with rimonabant were gastrointestinal, neurological, and psychiatric in nature. Serious adverse events were infrequent and almost equivalent to placebo. Overall discontinuation rates were similar across treatment groups, except discontinuation from adverse events, which occurred more frequently with 20 mg rimonabant versus placebo (most commonly, depressive disorders [1.9 vs. 0.8%], nausea [1.4 vs. 0.1%], mood alterations with depressive symptoms [1.0 vs. 0.6%], and anxiety [1.0 vs. 0.3%]). A thorough review of psychiatric and neurological adverse events was performed. CONCLUSIONS—In overweight/obese patients, 20 mg/day rimonabant produced weight loss and significant improvements in multiple cardiometabolic risk factors such as waist circumference, A1C, HDL cholesterol, and triglycerides. Rimonabant was generally well tolerated, with more frequently reported adverse events being gastrointestinal, neurological, and psychiatric in nature.
影响因子：
17.7
作者：
Posner, Kelly;Oquendo, Maria A.;Davies, Mark
通讯作者：
Davies, Mark