Association between metformin and vitamin B 12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized trials and observational studies
PubMed 27130885 · doi:10.1016/j.diabet.2016.03.008
What was done
Electronic databases (Cochrane Library, Scopus, CINAHL, Grey literature, PubMed Central, NICE guidelines, clinical trial registries) were searched from January 1957 to July 2013 for studies of any design evaluating metformin use in type 2 diabetes patients of any age or sex. Primary outcomes were serum vitamin B12 levels and prevalence, incidence, or risk of vitamin B12 deficiency.
What was found
Twenty-six papers met inclusion criteria. Ten of 17 observational studies found statistically significantly lower vitamin B12 levels in metformin users compared to non-users. Meta-analysis of four trials demonstrated a statistically significant mean reduction in vitamin B12 of 57 pmol/L (WMD fixed = -0.57, 95% CI: -35 to -79 pmol/L) after 6 weeks to 3 months of metformin treatment.
Why it matters
Demonstrates that metformin measurably lowers serum vitamin B12 levels within weeks to months of use, justifying routine monitoring for deficiency in treated patients with type 2 diabetes.
Limits
The meta-analysis included only four trials with short follow-up (6 weeks to 3 months). Total participant counts across studies are not reported in the abstract, and the search cut-off was July 2013. Clinical consequences such as neuropathy or anemia were not quantified.
Cited by
- supports Metformin can cause vitamin B12 deficiency.