WITHDRAWN: Metformin monotherapy for type 2 diabetes mellitus.
WITHDRAWN: Metformin monotherapy for type 2 diabetes mellitus.
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DOI：
10.1002/14651858.cd002966.pub4
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发表时间：
2015-09
期刊：
影响因子：
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通讯作者：
A. Sáenz;Inmaculada Fernandez-Esteban;Á. Mataix;Monica Ausejo Segura;Marta Roqué i Figuls;D. Moher
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文献类型：
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作者：
A. Sáenz;Inmaculada Fernandez-Esteban;Á. Mataix;Monica Ausejo Segura;Marta Roqué i Figuls;D. Moher
背景：二甲双胍是一种用于治疗2型糖尿病的降糖药物。2型糖尿病可能出现长期并发症：微血管（视网膜病变、肾病和神经病变）和大血管（中风、心肌梗死和周围血管疾病）。之前已经发表了两项荟萃分析，尽管只评估了次要结果。目的评价二甲双胍单药治疗对2型糖尿病患者死亡率、发病率、生活质量、血糖控制、体重、脂质水平、血压、胰岛素血症和蛋白尿的影响。检索策略研究是通过计算机检索多个电子数据库和手工检索已确定的相关试验的参考书目获得的。最近查册日期：2003年9月。符合以下纳入标准的试验：2型糖尿病、二甲双胍与任何其他口服干预、相关临床结果评估、随机分配。数据收集和分析两名审稿人使用标准的数据提取表格提取数据。数据在随机效应模型下汇总。二分类数据表示为相对风险。在可能的情况下，我们计算了风险差异（RD）和需要治疗的数量。我们收集了从基线变化的平均值和标准差的数据。然而，许多试验报告了终点数据。这一限制导致将结果表达为标准化平均差（SMD），并计算总体SMD。使用Z分数和i平方统计量检验异质性。采用亚组分析、敏感性分析和meta回归分析探讨异质性。我们纳入了29项试验，37组（5259名受试者），将二甲双胍（37组和2007名受试者）与磺脲类药物（13和1167名）、安慰剂（12和702名）、饮食（3和493名）、噻唑烷二酮类药物（3和132名）、胰岛素（2和439名）、美格列内酯类药物（2和208名）和葡萄糖苷酶抑制剂（2和111名）进行比较。9项研究报告了主要结果的数据。对于任何糖尿病相关结局（P = 0.009）和全因死亡率（P = 0.03），分配给二甲双胍强化血糖控制的肥胖患者比氯丙胺、格列本脲或胰岛素更有利。在糖尿病相关结局（P = 0.004）、糖尿病相关死亡（P = 0.03）、全因死亡率（P = 0.01）和心肌梗死（P = 0.02）方面，肥胖患者接受二甲双胍强化血糖控制比接受常规治疗的超重患者获益更大。二甲双胍单药治疗的患者在血糖控制、体重、血脂异常和舒张压方面显示出显著的益处。与安慰剂和饮食相比，二甲双胍对HbA1c有明显的益处；与磺脲类药物相比，在血糖控制、低密度脂蛋白胆固醇、BMI或体重方面有适度的益处。作者结论：二甲双胍可能是伴有超重或肥胖的2型糖尿病患者的首选治疗方案，因为它可以预防一些血管并发症和死亡率。二甲双胍在血糖控制方面产生有益的变化，并调节体重、血脂、胰岛素血症和舒张压。磺脲类药物、α -葡萄糖苷酶抑制剂、噻唑烷二酮类药物、美格列酮类药物、胰岛素和饮食对血糖控制、体重或血脂的益处不如二甲双胍。
BACKGROUND Metformin is an anti-hyperglycaemic agent used for the treatment of type 2 diabetes mellitus. Type 2 diabetes may present long-term complications: micro- (retinopathy, nephropathy and neuropathy) and macrovascular (stroke, myocardial infarction and peripheral vascular disease). Two meta-analyses have been published before, although only secondary outcomes were assessed. OBJECTIVES To assess the effects of metformin monotherapy on mortality, morbidity, quality of life, glycaemic control, body weight, lipid levels, blood pressure, insulinaemia, and albuminuria in patients with type 2 diabetes mellitus. SEARCH STRATEGY Studies were obtained from computerised searches of multiple electronic databases and hand searches of reference lists of relevant trials identified. Date of last search: September 2003. SELECTION CRITERIA Trials fulfilling the following inclusion criteria: Diabetes mellitus type 2, metformin versus any other oral intervention, assessment of relevant clinical outcome measures, use of random allocation. DATA COLLECTION AND ANALYSIS Two reviewers extracted data, using a standard data extraction form. Data were summarised under a random effects model. Dichotomous data were expressed as relative risk. We calculated the risk difference (RD), and the Number Needed to Treat, when it was possible. We collected data of mean and standard deviation from changes to baseline. However many trials reported end point data. This limitation lead to the expression of the results as standardised mean differences (SMD) and an overall SMD was calculated. Heterogeneity was tested for using the Z score and the I-squared statistic. Subgroup, sensitivity analysis and meta-regression were used to explore heterogeneity. MAIN RESULTS We included for analysis 29 trials with 37 arms (5259 participants), comparing metformin (37 arms and 2007 participants) with sulphonylureas (13 and 1167), placebo (12 and 702), diet (three and 493), thiazolidinediones (three and 132), insulin (two and 439), meglitinides (two and 208), and glucosidase inhibitors (two and 111). Nine studies reported data on primary outcomes. Obese patients allocated to intensive blood glucose control with metformin showed a greater benefit than chlorpropamide, glibenclamide, or insulin for any diabetes-related outcomes (P = 0.009), and for all-cause mortality (P = 0.03). Obese participants assigned to intensive blood glucose control with metformin showed a greater benefit than overweight patients on conventional treatment for any diabetes-related outcomes (P = 0.004), diabetes-related death (P = 0.03), all-cause mortality (P = 0.01), and myocardial infarction (P = 0.02). Patients assigned to metformin monotherapy showed a significant benefit for glycaemia control, weight, dyslipidaemia, and diastolic blood pressure. Metformin presents a strong benefit for HbA1c when compared with placebo and diet; and a moderated benefit for: glycaemia control, LDL cholesterol, and BMI or weight when compared with sulphonylureas. AUTHORS' CONCLUSIONS Metformin may be the first therapeutic option in the diabetes mellitus type 2 with overweight or obesity, as it may prevent some vascular complications, and mortality. Metformin produces beneficial changes in glycaemia control, and moderated in weight, lipids, insulinaemia and diastolic blood pressure. Sulphonylureas, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, insulin, and diet fail to show more benefit for glycaemia control, body weight, or lipids, than metformin.