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Long-term metformin usage and cognitive function among older adults with diabetes
Ng TP, Feng L, Yap KB, Lee TS, Tan CH, Winblad B.. Journal of Alzheimer's disease : JAD, 2014-01-01
Topic: Risk, prevention and care in population studies
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.
Key findings
- 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.
- 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).
Why it matters
In this study of 365 older people with diabetes, metformin use was linked to lower odds of cognitive impairment over 4 years, with a significant trend across duration of use. This is an observational association, so it does not show that metformin prevents or treats Alzheimer's disease.
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Study details
- Study designcross-sectional
- Participants204
- Effect sizeOR = 0.49; OR = 0.30; OR = 0.27
- Evidence strengthModerate
How this study scored 63/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 204 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 333 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.8 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 11.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 3 / 4 | Cited 69 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bengt G. Winblad: h-index 171 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24577463) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Ng, T. P., Feng, L., Yap, K. B., Lee, T. S., Tan, C. H., & Winblad, B. (2014). Long-term metformin usage and cognitive function among older adults with diabetes. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-131901
Vancouver
Ng TP, Feng L, Yap KB, Lee TS, Tan CH, Winblad B. Long-term metformin usage and cognitive function among older adults with diabetes. Journal of Alzheimer's disease : JAD. 2014. doi:10.3233/jad-131901. PMID: 24577463.
BibTeX
@article{ng2014-24577463,
author = {Ng, T. P. and Feng, L. and Yap, K. B. and Lee, T. S. and Tan, C. H. and Winblad, B.},
title = {{Long-term metformin usage and cognitive function among older adults with diabetes}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2014},
doi = {10.3233/jad-131901},
pmid = {24577463},
url = {https://doi.org/10.3233/jad-131901}
}
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