ArticlePloS one2011
Metformin treatment has no beneficial effect in a dose-response survival study in the SOD1(G93A) mouse model of ALS and is harmful in female mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review.Biomolecules · 2021Pooled it
- Insulin and Metformin are Associated With Reduced Risk of Amyotrophic Lateral Sclerosis.Chronic diseases and translational medicine · 2025Article
- Sephin1 suppresses ER stress-induced cell death by inhibiting the formation of PP2A holoenzyme.Cell death & disease · 2025Article
- Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Genetic Variation in Targets of Antidiabetic Drugs and Amyotrophic Lateral Sclerosis Risk.Biomedicines · 2024Article
- Article
- Radioprotective effect of the anti-diabetic drug metformin.PloS one · 2024Article
- A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19.Heliyon · 2023Review
- Type 2 diabetes, obesity, and risk of amyotrophic lateral sclerosis: A population-based cohort study.Brain and behavior · 2023Article
- Distinct Plasma Immune Profile in ALS Implicates sTNFR-II in pAMPK/Leptin Homeostasis.International journal of molecular sciences · 2023Article
- Altered Bioenergetics and Metabolic Homeostasis in Amyotrophic Lateral Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Metabolic Dysfunction in Motor Neuron Disease: Shedding Light through the Lens of Autophagy.Metabolites · 2022Review
- A chemogenomic approach is required for effective treatment of amyotrophic lateral sclerosis.Clinical and translational medicine · 2022Review
- Immune Signaling Kinases in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).International journal of molecular sciences · 2021Review
- The links between diabetes mellitus and amyotrophic lateral sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Review
- Compounds that extend longevity are protective in neurodegenerative diseases and provide a novel treatment strategy for these devastating disorders.Mechanisms of ageing and development · 2020Review
- Metformin inhibits RAN translation through PKR pathway and mitigates disease inProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Antidiabetics, statins and the risk of amyotrophic lateral sclerosis.European journal of neurology · 2020Article
- Genetics and Sex in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS): Is There a Link?International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAmyotrophic Lateral Sclerosis (ALS) is a devastating neurological disorder characterized by selective degeneration of upper and lower motor neurons. The primary triggers for motor neuron degeneration are unknown but inflammation, oxidative stress and mitochondrial defects have been identified as potential contributing factors. Metformin is an anti-type II diabetes drug that has anti-inflammatory and anti-oxidant properties, can bring about mitochondrial biogenesis and has been shown to attenuate pathology in mouse models of Huntington's disease and multiple sclerosis. We therefore hypothesized that it might increase survival in the SOD1(G93A) murine model of ALS. METHODOLOGY/PRINCIPAL
findingsTreatment of male and female SOD1(G93A) mice (n = ≥6 per sex) with 2 mg/ml metformin in the drinking water from 35 days, resulted in a significant increase in motor unit survival, as measured by in vivo electrophysiology at 100 days, in male EDL muscles (24+/-2 vs. 14+/-2 motor units, p<0.005) and female TA muscles (21+/-1 vs. 15+/-2 motor units, P = 0.0134). We therefore continued to test the effect of 0.5, 2 and 5 mg/ml metformin in the drinking water from 35 days on disease onset and progression (identified by twice weekly determination of weight and neurological score) as well as survival in male and female SOD1(G93A) mice (n = ≥14 per sex). Results for all groups were compared using Kaplan-Meier time to event analyses. In this survival study, metformin was unable to reduce pathology at any dose and had an unexpected dose-dependent negative effect on the onset of neurological symptoms (P = 0.0236) and on disease progression (P = 0.0362) in female mice. CONCLUSIONS/SIGNIFICANCE: This study suggests that metformin is a poor candidate for clinical trial in ALS patients and that the possibility of harmful effects of metformin in female ALS patients with type II diabetes should be investigated.
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Registered trials
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