Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, United Kingdom.
J Affect Disord. 2022 Aug 1;310:52-59. doi: 10.1016/j.jad.2022.04.156. Epub 2022 May 2.
The preclinical and clinical data regarding the efficacy of metformin as a pro-cognitive and anti-depressant therapy is mixed. We conducted a systematic review and meta-analysis of randomised controlled trials investigating the effects of metformin on cognition and depressive symptoms.
The study was conducted in accordance with PRISMA guidelines (PROSPERO identifier: CRD42020184547). PubMed and Web of Science were searched (inception through to May 6, 2020) for trials which measured the effects (change from baseline to end-of-treatment) of metformin on cognition and depressive symptoms, compared to either placebo or other oral antidiabetic therapies. When feasible, pooled meta-analytic estimates were provided using a random-effects model.
Eight studies met the inclusion criteria: four assessed only cognition, three assessed only depressive symptoms, and one study assessed both cognition and depressive symptoms. Results suggested that metformin was significantly superior to placebo in improving cognitive function in patients suffering with clinical conditions associated with cognitive impairment (SMD: 0.80; 95%CI: 0.46 to 1.15; p < 0.001; N = 2 studies; I = 0.0%). One study reported an association between improved cognition and depressive symptoms in a cohort of patients with type 2 diabetes mellitus and depression. Two studies investigating metformin versus pioglitazone showed a superior, but not significant, effect of pioglitazone on depressive symptoms (SMD: 1.56; 95%CI: -0.52 to 3.56; p = 0.13;I = 94.9%; N = 2 studies).
Assessment of risk of bias identified two studies as having "some concerns".
Our findings suggest that metformin might be re-purposed for the treatment of cognitive deficits in select clinical conditions.
二甲双胍作为一种认知增强和抗抑郁治疗药物的临床前和临床数据喜忧参半。我们对评估二甲双胍对认知和抑郁症状影响的随机对照试验进行了系统评价和荟萃分析。
该研究按照 PRISMA 指南（PROSPERO 标识符：CRD42020184547）进行。检索了 PubMed 和 Web of Science，以查找（从开始到 2020 年 5 月 6 日）评估二甲双胍对认知和抑郁症状影响的试验，与安慰剂或其他口服抗糖尿病药物相比。在可行的情况下，使用随机效应模型提供了汇总 meta 分析估计值。
八项研究符合纳入标准：四项仅评估认知，三项仅评估抑郁症状，一项研究同时评估认知和抑郁症状。结果表明，在患有与认知障碍相关的临床疾病的患者中，二甲双胍在改善认知功能方面明显优于安慰剂（SMD：0.80；95%CI：0.46 至 1.15；p<0.001；N=2 项研究；I=0.0%）。一项研究报告了患有 2 型糖尿病和抑郁症的患者队列中认知改善与抑郁症状之间的关联。两项比较二甲双胍与吡格列酮的研究表明，吡格列酮对抑郁症状的影响（SMD：1.56；95%CI：-0.52 至 3.56；p=0.13；I=94.9%；N=2 项研究）虽然有优势，但不显著。
风险偏倚评估确定了两项研究存在“一些关注”。
我们的研究结果表明，二甲双胍可能被重新用于治疗某些临床情况下的认知缺陷。
