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Investigating the pro-cognitive and anti-depressant efficacy of metformin: A systematic review and meta-analysis of randomised controlled trials

Nibber A, Singh H, Burnet P, Lennox B, Minichino A

Journal of affective disorders, 2022

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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; I2 = 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…

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