Meta-analysisindependent cross-checkabstract checked I-ODD-114 standard review
Metformin users have about twice the risk of low vitamin B12
Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis.
Overview
Yang W et al.. J Diabetes 2019 · PMID 30615306 · DOI 10.1111/1753-0407.12900
RR 2.09; B12 about 64 pmol/L lower.
Does the study support the specific claim? Yes · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Summarise metformin and B12 studies.
- How was the study done?
Meta-analysis of 31 studies.
- How many people, animals or samples were studied?
31 studies.
- What was actually found?
Lower B12 and more deficiency; no clear effect on anaemia or neuropathy.
- How large was the observed effect?
RR 2.09 (1.49-2.93).
- What do the results mean in everyday life?
Check B12 regularly when taking metformin.
- What are the study's limitations?
Mostly observational, heterogeneous.
- What does it say about Elawady's specific claim?
Supports the claim.
- Do the results apply to Germany and Europe?
High.
- What can explicitly not be concluded from this study?
That metformin should be stopped.
Scientific in-depth review
1. Full reference
- Authors
- Yang W et al.
- Journal
- J Diabetes
- Year
- 2019
- Identifier
- PMID 30615306 DOI 10.1111/1753-0407.12900
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Grant: Eisai China Inc. (PubMed record).
2. Research question
Is metformin use associated with vitamin B12 levels, anaemia and neuropathy in diabetes?
3. Study design and population
- Study design
- Meta-analysis – Meta-analysis of observational studies and trials
- Population
Patients with diabetes
- Country
International
- Period
Published before March 2018
- Sample size
31 studies
- Inclusion and exclusion criteria
English-language studies comparing metformin users and non-users
4. Methods and endpoints
- Exposure / intervention
Metformin
- Comparator
No metformin
- Endpoints
B12 deficiency, B12 concentration, anaemia, neuropathy
- Statistical methods
Pooled RR and mean differences; I2
5. Actual results
- Results
B12 deficiency RR 2.09 (1.49-2.93; I2 64%); B12 MD -63.70 pmol/L (-74.35 to -53.05; I2 87%), dependent on dose and duration; percentage decrease MD -14.68% (-17.98 to -11.39). No significant association with anaemia or neuropathy.
- Absolute risks
Not reported in abstract.
- Authors' conclusion
Metformin lowers B12 and increases deficiency risk; annual B12 assessment recommended.
6. Strengths
- Dose and duration dependence
- Several outcomes
7. Weaknesses
- High heterogeneity
- Mostly observational
- English only
- Industry grant (B12 supplement manufacturer)
8. Risk of bias
- Orienting tool
- AMSTAR 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Heterogeneity; observational data.
9. Assessment of the statistical interpretation
RR CI log-symmetric; MD CI symmetric (stats/C-ODD-07.py).
10. Relevance to the specific claim
Confirms the B12-lowering effect; shows clinical consequences (anaemia, neuropathy) are not consistently demonstrated.
11. Independent contrary findings
None against the B12 effect.
12. Transferability to Germany and Europe
High.
13. Overall methodological judgement
Consistent with RCT data (A-ODD-04): metformin lowers B12.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Clinical significance for neuropathy.