Background: Long-term use of clozapine for individuals with schizophrenia carries a high risk for developing metabolic abnormalities, especially clozapine-induced weight gain. Previous studies suggest that metformin can decrease clozapine-induced weight gain, but the sample sizes of most of these studies are relatively small.
Methods: We identified randomized controlled trials (RCTs) published prior to December 15, 2015 about the use of metformin to treat clozapine-induced weight gain in adults with schizophrenia by searching several English-language and Chinese-language databases. Two independent researchers did the screening and data extraction. We used Revman 5.3 to conduct the meta-analyses, assessed the risk of bias (RoB), and assessed the strength of the evidence using the Cochrane Grades of Recommendation, Assessment, Development, and Evaluation (GRADE).
Results: Six studies with a pooled sample of 207 treatment-group patients and 207 control-group patients were included -- three double-blind, placebo-controlled RCTs and three RCTs that did not use placebo controls and were not blinded. The meta-analysis found that compared to the control condition, patients receiving metformin experienced significantly greater reductions in body weight (mean difference [MD]=-2.89 kg, 95% CI: -4.20 to -1.59 kg) and body mass index (BMI) (MD=-0.81, 95% CI: -1.16 to -0.45), but there was no significant difference between the groups in the prevalence of side effects. Based on the GRADE scale, the strength of the evidence for the change in weight outcome was 'moderate' and that for the change in BMI outcome was 'high', but the strength of evidence about differences in side effects between groups was 'low' or 'very low'.
Conclusions: Adjunctive treatment with metformin appears to be effective for treating clozapine-induced weight gain and elevations in BMI in adult patients with schizophrenia. However, the quality of the evidence about the safety of this treatment is low, follow-up time in the available studies is relatively short, and half of the studies did not employ blinded assessment of outcome measures. Larger studies with placebo controls that follow patients for at least 24 weeks and that make blinded assessments of a range of relevant outcome measures (weight, BMI, blood lipids, insulin resistance, etc.) are needed to confirm these results.
背景: 精神分裂症患者长期使用氯氮平易出现代谢综合征，尤其是抗精神病药物引起的体重增加。既往研究表明，二甲双胍可以减少由氯氮平引起的体重增加，但大多数研究的样本量相对较小。.
方法: 通过检索多个中英文数据库，我们检索出在2015年12月15日之前发表的关于对成年精神分裂症患者使用二甲双胍治疗由氯氮平引起的体重增加的随机对照试验 (randomized controlled trial, RCT)。两位研究者独立进行筛选和数据提取。我们使用RevMan5.3软件进行Meta分析与偏倚风险评估，并采用Cochrane GRADE (Cochrane Grades of Recommendation, Assessment, Development, and Evaluation) 来评估证据质量。.
结果: 共纳入六项研究（合并样本量：2治疗组207例、对照组207例），其中三项研究是双盲、安慰剂对照的RCT，另三项RCT未在对照组中使用安慰剂，也未使用盲法。meta分析发现，与对照组相比服用二甲双胍的患者体重减轻更为显著 (MD=-2.89, 95% CI: -4.20 to-1.59)，并且体质量指数 (body mass index, BMI) 的降低也更为显著 (MD=-0.81, 95% CI: -1.16 to -0.45)，但两组不良反应的发生率之间无统计学差异。根据GRADE量表，关于体重结果变化的证据强度为“中等”，而关于BMI指数变化的证据强度是“高”，但关于组间不良反应差异的证据强度是“低” 或“非常低”。.
结论: 对成年精神分裂症患者使用二甲双胍辅助治疗可能对治疗由氯氮平引起的体重增加和BMI指数上升是有效的。然而，有关该治疗安全性的证据质量很低，现有研究的随访时间比较短，有一半的研究并没有对结果的进行盲法评估。我们需要进行更大样本量的研究，控制安慰剂效应并随访患者至少24周，且对一系列相关结果要进行盲法评估（体重、BMI 指数、血脂、胰岛素抵抗等），从而来证实这些结果。.
中文全文: 本文全文中文版从2016年04月25日起在http://dx. doi. org/10.11919/j. issn. 1002-0829.215071可供免费阅览下载.
Keywords: clozapine; clozapine-induced weight gain; meta-analysis; metformin; schizophrenia.