Vitamin B12 deficiency seen with long-term metformin use
Biochemical vitamin B12 deficiency and anemia were associated with long-term use of metformin, according to findings from the Diabetes Prevention Program Outcomes Study.
Jill P. Crandall, MD, professor of clinical medicine at Albert Einstein College of Medicine in Bronx, New York, and colleagues evaluated data from the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS) on 1,073 people assigned metformin and 1,082 assigned placebo for 3.2 years to determine the effect of long-term metformin on vitamin B12 levels. Participants assigned to metformin received open-label metformin for an additional 9 years. B12 levels were evaluated at 5 years (n = 857, placebo; n = 858, metformin) and 13 years (n = 756, placebo; n = 764, metformin).
Compared with placebo, the metformin group had a 10% lower mean B12 level (P = .02) and higher borderline-low vitamin B12 level (P < .01) at 5 years. Vitamin B12 deficiency was most prevalent among the metformin group and increased over time. Thirty-eight percent of the placebo group and 45% of the metformin group that were B12 deficient at 5 years remained deficient at 13 years. An increased risk for B12 deficiency was linked to years of metformin use (OR for B12 deficiency/year metformin use = 1.13; 95% CI, 1.06-1.2). The metformin group had a higher prevalence of anemia, which did not differ by B12 status. Among the metformin group, those with low B12 levels had a higher prevalence of neuropathy compared with those with normal or borderline levels (P = .03).
“Given that metformin is widely recommended as a first-line agent for the treatment of type 2 diabetes, the growing population of individuals who receive metformin for other indications (including high risk of diabetes, gestational diabetes, polycystic ovary syndrome), and the chronic nature of treatment of these conditions, understanding the potential adverse consequences of metformin treatment is essential,” the researchers wrote. “Long-term follow-up data from DPP/DPPOS support the evidence that metformin is associated with vitamin B12 deficiency, and routine measurement of vitamin B12 for metformin-treated individuals should be considered.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.