Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus
Abstract
Summary: Diabetes mellitus and depressive disorders are both common chronic diseases that increase functional disability and social burden. Cognitive impairment is a potentially debilitating feature of depression. Previous evidence indicates that the antidiabetic drug metformin could be suitable for diabetic patients with cognitive impairment. However, there is no direct evidence from clinical studies that metformin treatment improves cognitive function in diabetic patients suffering from depression. In the present study, 58 participants diagnosed with depression and type 2 diabetes mellitus ( T 2 DM ) were recruited and divided into two groups, one treated with metformin and the other treated with placebo for 24 weeks. Cognitive function, depressive behaviour and diabetes improvement were evaluated. Chronic treatment with metformin for 24 weeks improved cognitive performance, as assessed by the W echsler M emory S cale– R evised, in depressed patients with T 2 DM . In addition, metformin significantly improved depressive performance and changed the glucose metabolism in depressed patients with diabetes. Depressive symptoms were negatively correlated with cognitive performance in metformin‐treated participants. Furthermore, associations were observed between the parameters of blood glucose metabolism and the depression phenotype. These findings suggest that chronic treatment with metformin has antidepressant behavioural effects and that improved cognitive function is involved in the therapeutic outcome of metformin. The results of the present study also raise the possibility that supplementary administration of antidiabetic medications may enhance the recovery of depression, comorbid with T 2 DM , through improvements in cognitive performance.
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In a 24-week interventional study testing metformin relative to placebo in individuals with major depressive disorder and comorbid type II diabetes mellitus (n = 58), metformin was superior to placebo in improving depressive symptoms.
“The effect of metformin was superior to that of placebo in improving depressive symptoms in a sample of depressive patients with type II diabetes mellitus [122].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [122]
Metformin improved memory performance, assessed by the Wechsler Memory Scale-Revised, which was significantly related to a decrease in depressive symptoms.
“In addition, metformin improved memory performance (assessed by the Wechsler Memory Scale-Revised), which was significantly related to a decrease in depressive symptoms [122].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [122]
In a clinical trial of 58 participants with depression and T2DM, metformin improved cognitive performance over 24 weeks.
“In another clinical trial, 58 participants who had both depression and T2DM received either metformin or placebo for 24 weeks concluded that metformin improved cognitive performance (257).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [257]
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- Authors
- Guo, M., Mi, J., Jiang, Q., Xu, J., Tang, Y., Tian, G., & Wang, B.
- Affiliations
- Harbin Medical University (CN)
- Binzhou Medical University (CN)
- Division of Endocrinology Aerospace Center Hospital Aerospace Clinical Medical College Peking University Beijing China
- Department of Endocrinology Fourth Affiliated Hospital of Harbin Medical University Harbin China
- Corresponding author
- Guo, Min
- Venue
- Clinical and Experimental Pharmacology and Physiology
- Publisher
- Wiley
- Published
- 2014-09
- Volume
- 41
- Issue
- 9
- Pages
- 650-656
- ISSN
- 0305-1870 (ISSN-L)
- 1440-1681
- OpenAlex
- W2069494503
- Cited by
- 225
- References
- 46
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 9 · 2023: 27 · 2022: 30 · 2021: 28 · 2020: 34 · 2019: 21 · 2018: 22 · 2017: 17 · 2016: 8 · 2015: 6
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Experimental Pharmacology and Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Peking University
- Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province of China
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, antidepressant effects, depression, type 2 diabetes, cognitive impairment, cognitive function, glucose metabolism, depressive symptoms, comorbidities, antidiabetic drugs
- MeSH terms
- Adult, Antidepressive Agents, Cognition, Depression, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Psychiatric Status Rating Scales, Wechsler Scales
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