ArticlePloS one2019
Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 6 of them syntheses that pooled it.
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The trial behind it
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Who cites it
58 citing papers in PubMed, 6 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Effect of diabetes medications on the risk of developing dementia, mild cognitive impairment, or cognitive decline: A systematic review and meta-analysis.Journal of Alzheimer's disease : JAD · 2025Pooled it
- Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.Neurology · 2024Pooled it
- Association between metformin use and the risk of developing open-angle glaucoma among patients with diabetes: a retrospective cohort study and meta-analysis.International ophthalmology · 2024 · on this mapPooled 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
- Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis.BMJ open diabetes research & care · 2020 · on this mapPooled it
- Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study.Diabetologia · 2021Trial
- Diabetes, prediabetes, and mild cognitive impairment among older adults: the Hitachi Health Study II.Acta diabetologica · 2026Article
- Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Personalised Approach to the Management of Older People with Type 2 Diabetes Mellitus-A Comprehensive Narrative Review.Journal of personalized medicine · 2026Review
- Impact of ethnicity and antihyperglycemic medications on dementia incidence in older adults with type 2 diabetes.Endocrine connections · 2026Article
- Vascular cognitive impairment and dementia: Prevention, treatments, mechanisms and management options for the future.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Impact of metformin use on neurocognitive functions in older people: a systematic review and meta-analysis.Dementia & neuropsychologia · 2026Review
- Insulin use in diabetes association with cognitive impairment and dementia incidence.BMC pharmacology & toxicology · 2025Article
- Prevalence and Predictors of Cognitive Decline Among Diabetes Mellitus Patients Attending Jinja Regional Referral Hospital: A Cross-Sectional Study in Eastern Uganda.Health science reports · 2025Article
- New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study.The journal of prevention of Alzheimer's disease · 2025Article
- Impact of treatment modality on cognition in older adults with type 2 diabetes mellitus.Journal of family medicine and primary care · 2025Article
- Peripheral blood heat shock protein 27 correlates with information processing speed and executive function, potentially serving as a marker for mild cognitive impairment in patients with type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- The protective effects of insulin on the developing of dementia in chronic kidney disease patients with hypertension and diabetes: a population-based nationwide study.BMC nephrology · 2025Article
- Zi Shen Wan Fang repaired blood-brain barrier integrity in diabetic cognitive impairment mice via preventing cerebrovascular cells senescence.Chinese medicine · 2024Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
objectiveTo determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties. RESEARCH DESIGN AND
methodsFindings were pooled from 5 population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively. Findings were then pooled using meta-analytic techniques, including 3,590 individuals with diabetes for the prospective analysis.
resultsAfter adjusting for potential confounders including indices of glycemic control, insulin use was associated with increased risk of new-onset dementia (pooled HR (95% CI) = 1.58 (1.18, 2.12);p = 0.002) and with a greater decline in global cognitive function (β = -0.014±0.007;p = 0.045). The associations with incident dementia remained similar after further adjustment for renal function and excluding persons with diabetes whose treatment was life-style change only. Insulin use was not related to cognitive function nor to brain MRI measures. No significant associations were found between metformin or sulfonylurea use and outcomes of brain function and structure. There was no evidence of significant between-study heterogeneity.
conclusionsDespite its advantages in controlling glycemic dysregulation and preventing complications, insulin treatment may be associated with increased adverse cognitive outcomes possibly due to a greater risk of hypoglycemia.
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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.