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Metformin Cessation and Dementia Incidence
Zimmerman SC, Ferguson EL, Choudhary V, Ranatunga DK, Oni-Orisan A, Hayes-Larson E, et al.. JAMA Network Open, 2023-10-02
Topic: Risk, prevention and care in population studies
Importance Prior studies suggested that metformin may be associated with reduced dementia incidence, but associations may be confounded by disease severity and prescribing trends. Cessation of metformin therapy in people with diabetes typically occurs due to signs of kidney dysfunction but sometimes is due to less serious adverse effects associated with metformin. Exposures A total of 12 220 early terminators, individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR), were compared with routine metformin users, who had not yet terminated metformin treatment or had terminated (with or without restarting) after their first abnormal eGFR measurement. Results The final analytic sample consisted of 12 220 early terminators (5640 women [46.2%]; mean [SD] age at start of first metformin prescription, 59.4 [9.0] years) and 29 126 routine users (13 582 women [46.6%]; mean [SD] age at start of first metformin prescription, 61.1 [8.9] years). Early terminators had 1.21 times the hazard of dementia diagnosis compared with routine users (hazard ratio, 1.21; 95% CI, 1.12 to 1.30). In mediation analysis, contributions to this association by changes in HbA1c level or insulin use ranged from no contribution (0.00 years; 95% CI, -0.02 to 0.02 years) for insulin use at 5 years after termination to 0.07 years (95% CI, 0.02 to 0.13 years) for HbA1c level at 1 year after termination, suggesting that the association was largely independent of changes in HbA1c level and insulin usage. Conclusions and relevance In this study, terminating metformin treatment was associated with increased dementia incidence. This finding may have important implications for clinical treatment of adults with diabetes and provides additional evidence that metformin is associated with reduced dementia risk.
Key findings
- Importance Prior studies suggested that metformin may be associated with reduced dementia incidence, but associations may be confounded by disease severity and prescribing trends.
- Cessation of metformin therapy in people with diabetes typically occurs due to signs of kidney dysfunction but sometimes is due to less serious adverse effects associated with metformin.
- Exposures A total of 12 220 early terminators, individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR), were compared with routine metformin users, who had not yet terminated metformin treatment or had terminated (with or without restarting) after their first abnormal eGFR measurement.
- Results The final analytic sample consisted of 12 220 early terminators (5640 women [46.2%]; mean [SD] age at start of first metformin prescription, 59.4 [9.0] years) and 29 126 routine users (13 582 women [46.6%]; mean [SD] age at start of first metformin prescription, 61.1 [8.9] years).
- Early terminators had 1.21 times the hazard of dementia diagnosis compared with routine users (hazard ratio, 1.21; 95% CI, 1.12 to 1.30).
Why it matters
This cohort study found that people with diabetes who stopped metformin early, while their kidney function was still normal, had a higher hazard of dementia diagnosis compared with routine metformin users. It raises the possibility that continuing metformin may be linked to lower dementia risk, but the design cannot prove that metformin itself prevents dementia.
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Study details
- Study designcohort
- Participants41,346
- Effect sizeHR 1.21 (95% CI 1.12-1.30) for dementia after early metformin termination
- Evidence strengthModerate
Limitations
Observational; reasons for stopping metformin may themselves relate to health decline; single US health system.
How this study scored 65/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 64 of the 98 points we could judge it on, which is 65 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Network Open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over 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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 4 / 4 | 41,346 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 | 3 / 7 | Cited 27 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.4 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sarah F. Ackley: h-index 22 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37878309) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 64 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 64 of the 98 points we could judge it on is 65 out of 100. |
| Total | 65 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamanetworkopen.2023.39723
- PubMed: 37878309
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Zimmerman, S. C., Ferguson, E. L., Choudhary, V., Ranatunga, D. K., Oni-Orisan, A., Hayes-Larson, E., et al. (2023). Metformin Cessation and Dementia Incidence. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2023.39723
Vancouver
Zimmerman SC, Ferguson EL, Choudhary V, Ranatunga DK, Oni-Orisan A, Hayes-Larson E, et al. Metformin Cessation and Dementia Incidence. JAMA Network Open. 2023. doi:10.1001/jamanetworkopen.2023.39723. PMID: 37878309.
BibTeX
@article{zimmerman2023-37878309,
author = {Zimmerman, S. C. and Ferguson, E. L. and Choudhary, V. and Ranatunga, D. K. and Oni-Orisan, A. and Hayes-Larson, E. and others},
title = {{Metformin Cessation and Dementia Incidence}},
journal = {JAMA Network Open},
year = {2023},
doi = {10.1001/jamanetworkopen.2023.39723},
pmid = {37878309},
url = {https://doi.org/10.1001/jamanetworkopen.2023.39723}
}
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