Evidence map›Paper›PMID 24577463›Full record

ArticleJournal of Alzheimer's disease : JAD2014

Long-term metformin usage and cognitive function among older adults with diabetes.

Tze Pin Ng, Liang Feng, Keng Bee Yap, Tih Shih Lee, Chay Hoon Tan, Bengt Winblad

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02409238 (Insulin Resistance and Mild Cognitive Impairment), which is not on this map. Cited by 179 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed, 7 pooled it
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

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.

2 · The registry

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.

NCT02409238 phase4terminatedstarted 2015, after this paper: background citation

Insulin Resistance and Mild Cognitive Impairment (MCI) in Older Chinese Adults With Pre-Diabetes and Diabetes: Cognitive Effects of Lifestyle Intervention and Metformin Treatment in a Randomized Controlled Trial

Ran2015Enrolled105Registered outcomes16Posted comparisons0ConditionsDiabetes Mellitus, Type 2, Insulin Resistance, Mild Cognitive ImpairmentArmsIntensive Lifestyle Intervention, Metformin, Standard LIfestyle Recommendation
Open the trial in the graph
3 · Its place in the literature

Who cites it

179 citing papers in PubMed, 7 syntheses or guidelines pooled it, 324 citations in OpenAlex.

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  12. Longevity.Clinical medicine & research · 2026
    Review
  13. Article
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  17. Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026
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119 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Tze Pin NgGerontology Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Liang FengGerontology Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Keng Bee YapGerontology Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Department of Geriatric Medicine, Alexandra Hospital, Singapore, Singapore.
Tih Shih LeeGerontology Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Neuroscience Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
Chay Hoon TanGerontology Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Bengt WinbladKarolinska Institutet, Department of Neurobiology, Care Sciences and Society (NVS), Stockholm, Sweden.
National University of Singapore · SGAlexandra Hospital · SGDuke-NUS Medical School · SGKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Evidence strongly supports the important role of insulin resistance in cognitive decline and dementia and suggests that insulin sensitizers may protect against cognitive decline in diabetic and pre-diabetic individuals. Inconclusive results have been reported in clinical trials of rosiglitazone, an insulin sensitizer that also increases cardiovascular mortality risks. No study has yet reported a protective cognitive effect of metformin, an insulin-sensitizing biguanide widely used in diabetic patients. We studied 365 older persons aged 55 and over in the population-based Singapore Longitudinal Aging Study with diabetes who were followed up over 4 years. The odds ratios (OR) of association of metformin use (n = 204) versus non-use (n = 161) with cognitive impairment (Mini-Mental State Exam ≤ 23), and by duration: up to 6 years (n = 114) and more than 6 years (n = 90) were evaluated in cross-sectional and longitudinal multivariate analyses. Controlling for age, education, diabetes duration, fasting blood glucose, vascular and non-vascular risk factors, metformin use showed a significant inverse association with cognitive impairment in longitudinal analysis (OR = 0.49, 95% CI 0.25-0.95). Metformin use showed significant linear trends of association across duration of use in cross-sectional and longitudinal analyses (p = 0.018 and p = 0.002, respectively), with use for more than 6 years significantly associated with lowest risk of cognitive impairment in both cross-sectional analysis (OR = 0.30, 95% CI 0.11-0.80) and in longitudinal analysis (OR = 0.27, 95% CI 0.12-0.60). No significant interactive effects of metformin use with APOE-ε4, depression, or fasting glucose level were observed. Among individuals with diabetes, long-term treatment with metformin may reduce the risk of cognitive decline. Further studies should establish the role of hyperglycemia and insulin resistance, and the protective role of metformin in the risk of cognitive decline and dementia.

Indexed as

AgedAged, 80 and overCognition DisordersCross-Sectional StudiesDiabetes MellitusFemaleHumansHypoglycemic AgentsLinear ModelsLongitudinal StudiesMaleMetforminMiddle AgedMultivariate AnalysisOdds RatioProspective StudiesHypoglycemic AgentsMetforminCognitiondementiadiabetesinsulin resistancemetformin

Identifiers

PMID24577463
OpenAlexW1597817261

What OpenQuestion holds

Texttitle and abstract
Read underepoch 390

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.