SynthesisMedicine2020
Metformin therapy and cognitive dysfunction in patients with type 2 diabetes: A meta-analysis and systematic review.
Synthesis in Medicine, 2020. The graph read 7 numbers from its abstract, feeding 4 cells of the map: it . Cited by 29 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
In the subgroup analysis of various regions controlling for age, gender, education, diabetes course, complications, metformin administration and dosage, and follow-up time, metformin significantly improved cognitive dysfunction in patients in the Americas and Europe (HR 0.69; 95% CI [0.63, 0.74]), (HR 0.71; 95% CI [0.66, 0.76], respectively), while metformin did not significantly improve cognitive dysfunction in Asian patients (HR 0.99; 95% CI [0.96, 1.01]).
In the subgroup analysis of various regions controlling for age, gender, education, diabetes course, complications, metformin administration and dosage, and follow-up time, metformin significantly improved cognitive dysfunction in patients in the Americas and Europe (HR 0.69; 95% CI [0.63, 0.74]), (HR 0.71; 95% CI [0.66, 0.76], respectively), while metformin did not significantly improve cognitive dysfunction in Asian patients (HR 0.99; 95% CI [0.96, 1.01]).
In the subgroup analysis of various regions controlling for age, gender, education, diabetes course, complications, metformin administration and dosage, and follow-up time, metformin significantly improved cognitive dysfunction in patients in the Americas and Europe (HR 0.69; 95% CI [0.63, 0.74]), (HR 0.71; 95% CI [0.66, 0.76], respectively), while metformin did not significantly improve cognitive dysfunction in Asian patients (HR 0.99; 95% CI [0.96, 1.01]).
Read, but not usablea number the graph found but could not read as for or against
The use of insulin aggravated cognitive dysfunction (HR 1.34; 95% CI [1.24, 1.43]).
Metformin significantly reduced the occurrence of cognitive dysfunction in patients with T2D (HR 0.90; 95% CI [0.88, 0.92]).
Compared with other hypoglycemic drugs, sulfonylureas also improved cognitive dysfunction (HR 0.92; 95% CI [0.88, 0.95]).
Thiazolidinediones gave no statistically significant improvement in cognitive dysfunction (HR 0.97; 95% CI [0.87, 1.07]).
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Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
Metformin×quality of life & behaviour
No readable resultOpen on the map →What to test next →No other readable study in this cell yet. This paper is the evidence.
Insulin×quality of life & behaviour
No readable resultOpen on the map →What to test next →4 readable studies in this cell: 1 favour the treatment, 2 find no difference, 1 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Sulfonylureas & glinides×quality of life & behaviour
No readable resultOpen on the map →What to test next →No other readable study in this cell yet. This paper is the evidence.
Thiazolidinediones×quality of life & behaviour
No readable resultOpen on the map →What to test next →No other readable study in this cell yet. This paper is the evidence.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 3 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Metformin and Cognitive Performance in Patients With Type 2 Diabetes: An Umbrella Review.Neuropsychopharmacology reports · 2025Pooled it
- Metformin use is associated with a reduced risk of cognitive impairment in adults with diabetes mellitus: A systematic review and meta-analysis.Frontiers in neuroscience · 2022Pooled it
- Gray Matter Abnormalities in Type 1 and Type 2 Diabetes: A Dual Disorder ALE Quantification.Frontiers in neuroscience · 2021Pooled it
- Metformin Ameliorates Diabetes-Associated Cognitive Dysfunction via p53/Parkin-Mediated Mitophagy.Diabetes, obesity & metabolism · 2026Article
- Impact of antidiabetic therapy on cognitive function in patients with type 2 diabetes and Alzheimer's disease: A comprehensive analysis.Journal of Alzheimer's disease : JAD · 2025Article
- Risk Factors, Pathological Changes, and Potential Treatment of Diabetes-Associated Cognitive Dysfunction.Journal of diabetes · 2025Review
- Metformin's Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review.International journal of molecular sciences · 2025Review
- Role of glucagon-like peptide-1 receptor agonists in Alzheimer's disease and Parkinson's disease.Journal of biomedical science · 2024Review
- Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden.Aging cell · 2024Article
- Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records.BMJ open diabetes research & care · 2024 · on this mapObservational
- Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19.Brain communications · 2024Review
- Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases.International journal of molecular sciences · 2023Review
- Type 2 Diabetes (T2DM) and Parkinson's Disease (PD): a Mechanistic Approach.Molecular neurobiology · 2023Review
- Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis.Pharmacological reports : PR · 2023Review
- Metformin alleviates neurocognitive impairment in aging via activation of AMPK/BDNF/PI3K pathway.Scientific reports · 2022Article
- Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
- Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment.Frontiers in pharmacology · 2022Article
- Insights into Cognitive Brain Health in Chronic Kidney Disease.Gerontology & geriatrics : research · 2022Article
- Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway.BMC neuroscience · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundType 2 diabetes (T2D) is a risk factor for cognitive dysfunction. The relationship between metformin therapy and cognitive function in patients with T2D is unknown. Therefore, we determined the relationship between metformin therapy and cognitive function in patients with T2D using a meta-analysis.
methodsWe systematically searched the Cochrane library, PubMed, and Embase to identify studies showing correlations, and we calculated hazard ratios (HRs).
resultsWe identified 10 studies including 254,679 participants. Metformin significantly reduced the occurrence of cognitive dysfunction in patients with T2D (HR 0.90; 95% CI [0.88, 0.92]). Compared with other hypoglycemic drugs, sulfonylureas also improved cognitive dysfunction (HR 0.92; 95% CI [0.88, 0.95]). Thiazolidinediones gave no statistically significant improvement in cognitive dysfunction (HR 0.97; 95% CI [0.87, 1.07]). The use of insulin aggravated cognitive dysfunction (HR 1.34; 95% CI [1.24, 1.43]). In the subgroup analysis of various regions controlling for age, gender, education, diabetes course, complications, metformin administration and dosage, and follow-up time, metformin significantly improved cognitive dysfunction in patients in the Americas and Europe (HR 0.69; 95% CI [0.63, 0.74]), (HR 0.71; 95% CI [0.66, 0.76], respectively), while metformin did not significantly improve cognitive dysfunction in Asian patients (HR 0.99; 95% CI [0.96, 1.01]).
conclusionsMetformin significantly improved cognitive dysfunction in patients with T2D. Sulfonylureas also improved cognitive dysfunction. Thiazolidinediones had no significant effect on cognitive dysfunction. The use of insulin aggravated cognitive dysfunction. Metformin improved cognitive dysfunction more significantly in patients in the Americas and Europe than in Asia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.