Metformin Use Is Associated With Better Cognitive Performance in Older Adults With Type 2 Diabetes: Exploratory Analysis of Vitamin B12 and Methylmalonic Acid Pathways in NHANES 2011–2014
Authors' conclusion
Metformin is associated with better cognition in older T2DM adults. The association was not statistically explained by B12 or MMA. The benefit was concentrated in younger-old and cognitively vulnerable subgroups.
Study context
- Population
- Adults aged ≥60 years with T2D, NHANES 2011–2014
- Participants
- 587 adults
- Exposure
- Metformin vs other non-insulin antidiabetics
- Metforminn = 408
- Other non-insulin antidiabeticsn = 179reference
- Outcome
- Digit Symbol Substitution Test (DSST)
Methodological detailsactive-comparator design, exploratory causal mediation analysis, nationally representative sample
- Active-comparator design
- Exploratory causal mediation analysis
- Nationally representative sample
Main finding
As reported in the abstract
DSST score
Metformin
47.5
Other non-insulin antidiabetics
39.5
Metformin vs Other non-insulin antidiabeticsFully adjusted difference, points (95% CI)P value
Fully adjusted regression
3.75(−0.06 to 7.55)
P = 0.053- Multiple imputation
- β 3.49; P = 0.006
Observational data: associations, not effects.
Further findings
Serum vitamin B12
P = 0.026
- Digit Symbol Substitution Test (DSST) by age subgroup · benefit concentrated in adults aged 60-69 years
- interaction p = 0.003
Mediation by B12/MMA
- Proportion of effect direct and B12/MMA-independent across mediation frameworks
- 95.1%
DSST by age subgroup
- Benefit concentrated in lower DSST quantiles
Original publication
Metformin Use Is Associated With Better Cognitive Performance in Older Adults With Type 2 Diabetes: Exploratory Analysis of Vitamin B12 and Methylmalonic Acid Pathways in NHANES 2011–2014. Diabetes Obes Metab. Published 28 September 2026. doi:10.
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