Randomised controlled trialcited by the Tayebat archiveabstract only checked A-ODD-06 standard review
Metformin and B12 over 13 years
Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study.
Overview
Aroda VR et al.. J Clin Endocrinol Metab 2016 · PMID 26900641 · DOI 10.1210/jc.2015-3754
Each year of metformin raised the odds of B12 deficiency by about 13%.
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?
Long-term metformin and B12 deficiency
- How was the study done?
Secondary analysis of RCT and open-label extension (DPP/DPPOS)
- How many people, animals or samples were studied?
2,155 randomised (1,082 + 1,073); B12 measured in 1,715 at 5 years and 1,520 at 13 years; People with prediabetes and overweight
- What was actually found?
OR 1.13 per year.
- How large was the observed effect?
OR 1.13 (1.06-1.20)
- What do the results mean in everyday life?
Monitor B12.
- What are the study's limitations?
Placebo group partly unblinded after DPP; Secondary analysis
- What does it say about Elawady's specific claim?
Supports C-ODD-07.
- Do the results apply to Germany and Europe?
US data.
- What can explicitly not be concluded from this study?
Clinical harm magnitude.
Scientific in-depth review
1. Full reference
- Authors
- Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, Bray GA, Schade DS, Temprosa MG, White NH, Crandall JP, Diabetes Prevention Program Research Group
- Journal
- J Clin Endocrinol Metab
- Year
- 2016
- Identifier
- PMID 26900641 DOI 10.1210/jc.2015-3754 · PMC4880159
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract; grants: NCATS NIH HHS, NIDDK NIH HHS
2. Research question
Long-term metformin and B12 deficiency
3. Study design and population
- Study design
- Randomised controlled trial – Secondary analysis of RCT and open-label extension (DPP/DPPOS)
- Population
People with prediabetes and overweight
- Country
USA
- Period
Up to 13 years
- Sample size
2,155 randomised (1,082 placebo + 1,073 metformin); B12 measured in 1,715 at 5 years (857 + 858) and 1,520 at 13 years (756 + 764)
- Inclusion and exclusion criteria
As described in the abstract; details not available in abstract.
4. Methods and endpoints
- Exposure / intervention
Metformin 850 mg twice daily
- Comparator
Placebo
- Endpoints
B12 deficiency, anaemia, neuropathy
- Statistical methods
Logistic models
5. Actual results
- Results
Low B12 (<=203 pg/mL) 4.3 vs 2.3% at 5 years (P=0.02), 7.4 vs 5.4% at 13 years (P=0.12). Low+borderline 19.1 vs 9.5% (5 y), 20.3 vs 15.6% (13 y). OR 1.13 per year of use. Anaemia higher with metformin; neuropathy higher in metformin users with low B12.
- Absolute risks
not reported
- Authors' conclusion
Long-term metformin associated with biochemical B12 deficiency and anaemia; routine testing should be considered.
6. Strengths
- Randomised origin
- Long follow-up
7. Weaknesses
- Placebo group partly unblinded after DPP
- Secondary analysis
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Post-randomisation open-label phase.
9. Assessment of the statistical interpretation
13-year strict-cutoff difference not significant.
10. Relevance to the specific claim
Supports C-ODD-07.
11. Independent contrary findings
12. Transferability to Germany and Europe
US data.
13. Overall methodological judgement
Consistent.
| 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) | essentially correct but incomplete |
14. Open questions
None beyond those stated.
15. Linked fact checks
- Every major class of glucose-lowering drug (metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists) carries a documented signal of serious harm in the peer-reviewed literature. – Studies supporting the claim
- Long-term metformin lowers vitamin B12 and increases B12 deficiency (de Jager RCT: -19%, +7.2 percentage points deficiency over 4.3 years; DPPOS confirms). – Studies supporting the claim
Use by the Tayebat archive
Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.
- What the archive says about the study
Narrative: the 13-year DPPOS follow-up confirmed the cumulative risk.
- A. What was actually studied?
Long-term metformin and B12 deficiency
- B. What did the authors find?
OR 1.13 per year.
- C. What conclusions do the authors themselves draw?
Long-term metformin associated with biochemical B12 deficiency and anaemia; routine testing should be considered.
- D. What does the archive derive from it?
Support for metformin harm.
- E. Is this derivation scientifically justified?
Largely justified; archive omits the non-significant 13-year strict cutoff.
- Adequacy of the interpretation (by the archive)
- essentially correct but incomplete