SynthesisBMJ open diabetes research & care2020

Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis.

Fan Ping, Ning Jiang, Yuxiu Li

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in BMJ open diabetes research & care, 2020. The graph read 2 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 53 papers, 4 of them syntheses that pooled it.

2numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 4 pooled it
field-weighted citation impact
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.

Read, but not usablea number the graph found but could not read as for or against

Pharmacokinetics & dosingcomparator not stated · t2dfeeds one cell of the map
OR 1.040.92 to 1.17
Meta-analysis found there was no significant effect on incidence of all the subtypes of NDs with metformin exposure (OR 1.04, 95% CI 0.92 to 1.17).
Pharmacokinetics & dosingcomparator not stated · t2dfeeds 2 cells of the map
OR 1.661.14 to 2.42
However, metformin monotherapy was associated with a significantly increased risk of PD incidence compared with non-metformin users or glitazone users (OR 1.66, 95% CI 1.14 to 2.42).

clause the extractor read what became the number

2 · Its place on the map

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.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

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×pharmacokinetics & dosing

No readable resultOpen on the map →What to test next →

2 readable studies in this cell: 0 favour the treatment, 2 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT00631488146 enrolled · 2008
Δ 22.6-0.60 to 45.8
NCT0200488674 enrolled · 2006
Δ -6.60-34.0 to 20.8

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Thiazolidinediones×pharmacokinetics & dosing

No readable resultOpen on the map →What to test next →

No other readable study in this cell yet. This paper is the evidence.

Belief with this paperNo claim has been compiled for this cell yet.
4 · 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

53 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Article
  6. Article
  7. Article
  8. Article
  9. Observational
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025
    Review
  17. Review
  18. Review
  19. Review
  20. Review
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

3 authors.

Fan PingDepartment of Endocrinology, Peking Union Medical College Hospital, Beijing, China.
Ning JiangDepartment of Endocrinology, Peking Union Medical College Hospital, Beijing, China.
Yuxiu LiDepartment of Endocrinology, Peking Union Medical College Hospital, Beijing, China liyuxiu@medmail.com.cn.ORCID 0000-0001-7500-0855

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

BACKGROUND AND

aimsAging becomes a growing global concern with an increased risk of neurodegenerative diseases (NDs) that mainly consist of cognitive decline and Parkinson disease (PD). As the most commonly prescribed antidiabetic drug, metformin has been shown to have inconsistent roles in the incidence of NDs. We performed a systematic review and meta-analysis of observational studies to evaluate the effect of metformin exposure on onset of NDs.

methodsThe observational studies that investigated the associations between metformin and the incidence of NDs were searched in MEDLINE, Embase and Cochrane Library databases. A random-effect model was performed using STATA to calculate the combined ORs.

resultsIn total, 23 comparisons out of 19 studies with 285 966 participants were included. Meta-analysis found there was no significant effect on incidence of all the subtypes of NDs with metformin exposure (OR 1.04, 95% CI 0.92 to 1.17). However, metformin monotherapy was associated with a significantly increased risk of PD incidence compared with non-metformin users or glitazone users (OR 1.66, 95% CI 1.14 to 2.42).

conclusionMetformin has failed to demonstrate a beneficial effect on NDs. In addition, it may increase the risk of PD development. In light of current results, how metformin would impact NDs, especially the potential risk of PD, needs to be scrutinized. The underlying mechanisms are vital to achieve some more profound understanding on the regimen. TRIAL REGISTRATION NUMBER: CRD 42019133285.

Indexed as

Diabetes Mellitus, Type 2MetforminNeurodegenerative DiseasesThiazolidinedionesHumansHypoglycemic AgentsHypoglycemic AgentsMetforminThiazolidinedionesalzheimer diseasecentral nervous Systemdementiametformin

Identifiers

PMID32719079
PMCPMC7390234

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.