Scheen André J, Finer Nick, Hollander Priscilla, Jensen Michael D, Van Gaal Luc F
Division of Diabetes, Nutrition and Metabolic Disorders, CHU Sart Tilman, University of Liege, Liege, Belgium.
Lancet. 2006 Nov 11;368(9548):1660-72. doi: 10.1016/S0140-6736(06)69571-8.
Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas.
1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00029848.
692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 vs placebo). Rimonabant was generally well tolerated. The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group, mainly due to depressed mood disorders, nausea, and dizziness.
These data indicate that 20 mg/day rimonabant, in combination with diet and exercise, can produce a clinically meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas.
利莫那班是一种选择性大麻素1型受体阻滞剂，可减轻非糖尿病超重或肥胖患者的体重，并改善心血管和代谢风险因素。RIO-糖尿病试验的目的是评估利莫那班对二甲双胍或磺脲类药物控制不佳的超重或肥胖2型糖尿病患者的疗效和安全性。
1047例超重或肥胖的2型糖尿病患者（体重指数27-40kg/m²），糖化血红蛋白（HbA1c）浓度为6.5-10.0%（基线时平均7.3%[标准差0.9]），已接受二甲双胍或磺脲类单药治疗，给予轻度低热量饮食并建议增加体育活动，随机分配接受安慰剂（n=348）、5mg/天利莫那班（360例）或20mg/天利莫那班（339例）治疗1年。5mg/天组有2例患者未接受双盲治疗，因此未纳入最终分析。主要终点是治疗1年后相对于基线的体重变化。分析采用意向性分析。该试验已在ClinicalTrials.gov注册，编号为NCT00029848。
692例患者完成了1年的随访；1年后每组人数大致相同。1年后，两个利莫那班组的体重减轻均显著大于安慰剂组（安慰剂组：-1.4kg[标准差3.6]；5mg/天组：-2.3kg[4.2]，与安慰剂组相比p=0.01；20mg/天组：-5.3kg[5.2]，与安慰剂组相比p<0.0001）。利莫那班总体耐受性良好。导致停药的不良事件发生率在20mg/天利莫那班组略高，主要原因是情绪低落、恶心和头晕。
这些数据表明，20mg/天利莫那班联合饮食和运动，可使二甲双胍或磺脲类药物控制不佳的超重或肥胖2型糖尿病患者的体重在临床上显著减轻，并改善糖化血红蛋白以及一些心血管和代谢风险因素。
