Finer N, Ryan D H, Renz C L, Hewkin A C
Wellcome Trust Clinical Research Facility, Cambridge, UK.
Diabetes Obes Metab. 2006 Mar;8(2):206-13. doi: 10.1111/j.1463-1326.2005.00481.x.
Early weight loss is generally considered to predict long-term weight outcome in obese patients, and this is reflected in prescribing guidelines for antiobesity drugs. For example, the current prescribing guidelines for the antiobesity drug, sibutramine, indicate that if patients have not lost 2 kg (or 4 lb) in the first 4 weeks of treatment with sibutramine 10 mg, the physician should re-evaluate the therapy, which may result in increasing the dose to 15 mg or discontinuation. This regimen may deny treatment to a large group of patients who might otherwise benefit, particularly patients with type 2 diabetes who often find it more difficult to lose weight than non-diabetic obese individuals.
We have re-analysed pooled data from seven randomized, controlled studies of sibutramine-induced weight loss and maintenance in which patients (n = 928; 75% female) had taken sibutramine 10 or 15 mg continuously for 12 months, in order to determine the predictors of success in weight loss (defined as loss of at least 5% of initial body weight at Month 12) in both diabetic and non-diabetic patients. Sensitivity and specificity analyses were used to calculate optimal predictive values.
In both diabetic and non-diabetic patients, weight loss of 4 kg at 3 months was identified as the optimal predictor for achieving at least 5% weight loss at 12 months. This target was associated with the best average values for sensitivity, specificity and accuracy, as well as high positive (78% vs. 84% for non-diabetics and 76% vs. 85% for diabetics, compared to existing guidelines target of 2 kg after 1 month treatment) and negative predictive values (63% vs. 71% for non-diabetics; 52% vs. 70% for diabetics).
Sibutramine, in conjunction with diet and exercise, should be continued for at least 3 months (providing there are no adverse effects) to determine whether or not patients are likely to achieve a clinically valid outcome at 1 year. This highlights the need to ensure that regulatory restrictions reflect the needs of clinical practice.
早期体重减轻通常被认为可预测肥胖患者的长期体重结果，这一点在抗肥胖药物的处方指南中有所体现。例如，当前抗肥胖药物西布曲明的处方指南指出，如果患者在使用10毫克西布曲明治疗的前4周内体重未减轻2千克（或4磅），医生应重新评估治疗方案，这可能导致将剂量增加至15毫克或停药。这种方案可能会使一大批原本可能受益的患者得不到治疗，尤其是2型糖尿病患者，他们往往比非糖尿病肥胖个体更难减肥。
我们重新分析了七项关于西布曲明诱导体重减轻及维持的随机对照研究的汇总数据，这些研究中的患者（n = 928；75%为女性）连续12个月服用10或15毫克西布曲明，以确定糖尿病和非糖尿病患者体重减轻成功（定义为在第12个月时体重减轻至少初始体重的5%）的预测因素。使用敏感性和特异性分析来计算最佳预测值。
在糖尿病和非糖尿病患者中，3个月时体重减轻4千克被确定为12个月时体重减轻至少5%的最佳预测因素。该目标与敏感性、特异性和准确性的最佳平均值相关，以及高阳性预测值（非糖尿病患者为78%对84%，糖尿病患者为76%对85%，而现有指南中治疗1个月后体重减轻2千克的目标为78%对84%）和阴性预测值（非糖尿病患者为63%对71%；糖尿病患者为52%对70%）。
西布曲明与饮食和运动相结合，应持续至少3个月（前提是没有不良反应），以确定患者是否有可能在1年内取得临床有效结果。这凸显了确保监管限制反映临床实践需求的必要性。
