ArticleBehavioural brain research2016
Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice.
Article in Behavioural brain research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Metformin for knee osteoarthritis in overweight and obese adults: a systematic review and meta-analysis of efficacy, safety, and disease-modifying anti-inflammatory potential.Inflammopharmacology · 2026Pooled it
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Effect of a Comprehensive Intervention on Plasma BDNF in Patients with Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2017Trial
- Exploring the impacts of type 2 diabetes and metformin use on Parkinson's disease: Mendelian randomization analysis and a national cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Metformin versus DPP-4 inhibitors and risk of parkinsonism in type 2 diabetes: an active-comparator cohort study with a landmark design.Diabetology & metabolic syndrome · 2026Article
- Repurposing Antidiabetic Medications for Parkinson's Disease: Focus on Biomarker Strategies for Disease Modification.International journal of molecular sciences · 2026Review
- Metformin Ameliorates Cognitive Deficits and Neuroinflammation in a Mouse Model of Familial Hypercholesterolemia.Neurochemical research · 2026Article
- Metformin use on the risks of depression and anxiety in people with type 2 diabetes.Communications medicine · 2025Article
- Article
- Metformin, Cognitive Function, and Changes in the Gut Microbiome.Endocrine reviews · 2024Review
- Novel targets and therapies of metformin in dementia: old drug, new insights.Frontiers in pharmacology · 2024Review
- Comparative Efficacy of Metformin and Glimepiride in Modulating Pharmacological Network to Increase BDNF Levels and Benefit Type 2 Diabetes-Related Cognitive Impairment.Biomedicines · 2023Article
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
- Metformin Attenuates Tau Pathology in Tau-Seeded PS19 Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.Drug design, development and therapy · 2023Review
- NRF2 and Diabetes: The Good, the Bad, and the Complex.Diabetes · 2022Review
- Diabetes: Risk factor and translational therapeutic implications for Alzheimer's disease.The European journal of neuroscience · 2022Article
- Brain Metabolic Alterations in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Promise of metformin for preventing age-related cognitive dysfunction.Neural regeneration research · 2022Review
- Investigation of the Molecular Role of Brain-Derived Neurotrophic Factor in Alzheimer's Disease.Journal of molecular neuroscience : MN · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Long-term use of anti-diabetic agents has become commonplace as rates of obesity, metabolic syndrome and diabetes continue to escalate. Metformin, a commonly used anti-diabetic drug, has been shown to have many beneficial effects outside of its therapeutic regulation of glucose metabolism and insulin sensitivity. Studies on metformin's effects on the central nervous system are limited and predominantly consist of in vitro studies and a few in vivo studies with short-term treatment in relatively young animals; some provide support for metformin as a neuroprotective agent while others show evidence that metformin may be deleterious to neuronal survival. In this study, we examined the effect of long-term metformin treatment on brain neurotrophins and cognition in aged male C57Bl/6 mice. Mice were fed control (C), high-fat (HF) or a high-fat diet supplemented with metformin (HFM) for 6 months. Metformin decreased body fat composition and attenuated declines in motor function induced by a HF diet. Performance in the Morris water maze test of hippocampal based memory function, showed that metformin prevented impairment of spatial reference memory associated with the HF diet. Quantitative RT-PCR on brain homogenates revealed decreased transcription of BDNF, NGF and NTF3; however protein levels were not altered. Metformin treatment also decreased expression of the antioxidant pathway regulator, Nrf2. The decrease in transcription of neurotrophic factors and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation.
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