Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial.
Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial.
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DOI：
10.1136/thoraxjnl-2015-208035
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发表时间：
2016-07
期刊：
影响因子：
10
通讯作者：
Metformin in COPD Trial Team
中科院分区：
文献类型：
--
作者：
Hitchings AW;Lai D;Jones PW;Baker EH;Metformin in COPD Trial Team
慢性阻塞性肺疾病的严重恶化通常与高血糖有关，高血糖预示着不良后果。二甲双胍是一种公认的抗糖尿病高血糖药，可能具有抗炎作用，但其对COPD的作用尚不清楚。我们研究了加速二甲双胍治疗重度COPD急性加重期，主要是为了证实或驳斥其抗高血糖作用，其次是探讨其对炎症和临床结局的影响。这是一项多中心、随机、双盲、安慰剂对照试验，测试了年龄35岁、因慢性阻塞性肺疾病恶化而住院的非糖尿病患者加速二甲双胍治疗的效果。参与者被分配到2：1的比例，接受1 月的二甲双胍治疗，迅速增加到2 g/d，或匹配的安慰剂。主要终点是住院期间的平均血糖浓度。次要终点包括果糖胺和C反应蛋白(CRP)浓度，以及COPD评估测试和慢性肺病恶化工具的评分。52名参与者(平均(±SD)年龄67±9 岁)被随机分组(34名服用二甲双胍，18名服用安慰剂)。所有患者均被纳入主要终点分析。二甲双胍组和安慰剂组的平均血糖浓度分别为7.1±0.9和8.0±3.3 /L(差值−0.9 /L，95%可信区间−2.1~+0.3；p=0.273)。在任何次要终点上，组间均未观察到显著差异。不良反应，特别是胃肠道反应，在接受二甲双胍治疗的参与者中更为常见。二甲双胍不能改善因COPD加重而住院的非糖尿病患者的血糖浓度升高，对CRP或临床结果也没有可检测到的影响。ISRCTN66148745和NCT01247870。
Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. ISRCTN66148745 and NCT01247870.