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Metformin and Vitamin B₁₂ Deficiency

Evidence suggests that metformin lowers vitamin B₁₂ levels in patients with diabetes.

Observational studies have suggested that metformin causes vitamin B₁₂ deficiency in some patients; researchers have proposed several possible mechanisms whereby metformin might interfere with B₁₂ absorption. Understanding this interaction is important, because B₁₂ deficiency could exacerbate neuropathic symptoms in patients with diabetes.

In this prospective case-control study, Canadian investigators identified 122 type 2 diabetic patients with peripheral neuropathy: Half had taken metformin for at least 6 months, and half had never received metformin. Otherwise, clinical characteristics of the groups were similar.

Median serum B₁₂ level was significantly lower in the metformin group than in the no-metformin group (231 vs. 486 pmol/L). Metformin recipients also had significantly higher levels of homocysteine and methylmalonic acid (markers of B₁₂ deficiency) and significantly worse scores on standardized clinical assessments of severity of neuropathy. In multivariate analyses controlled for age, duration of diabetes, and glycosylated hemoglobin (HbA_1c) level, metformin therapy was associated independently with worse neuropathic symptoms.

Comment: This study strengthens the case for an effect of metformin therapy on vitamin B₁₂ levels. The analysis also suggests that this interaction worsens neuropathy, but confounding by unknown factors could be responsible for this observation. In one randomized placebo-controlled trial, metformin lowered B₁₂ levels (J Intern Med 2003; 254:455); now, we need a trial to determine whether B₁₂ supplementation is beneficial for diabetic patients who take metformin.

— Allan S. Brett, MD

Published in Journal Watch General Medicine February 25, 2010

Citation(s):

Wile DJ and Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care 2010 Jan; 33:156.

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Reader Remarks:

Review and add to remarks on this article

• B12 deficiency and metformin
  Scott A Joseph, MD, 26 Feb 2010 12:22 PM EST
  The risk of deficiency and the need for monitoring when on metformin is noted in the 2010 PDR on page... [more]
• Metformin & worsened diabetic peripheral neuropathy.
  Dr. J. Sil, India., 26 Feb 2010 12:22 PM EST
  It is a very important observation. However, we may not be well advised at this stage to avoid Metformin. Supplementation... [more]
• Metformin and Diabetic neuropathy
  Dr. Abid Ahmed, Royal Commission Medical Center, Yanbu, Saudi Arabia, 1 Mar 2010 2:43 PM EST
  This issue of B12 dificiency due to Metformin is a well known fact, since many years. However clinical implication of... [more]
• Metformin and Vit B12
  Carol T. O'Connor, RN, MSN, Adjunct Faculty;former DM Case Manager, 1 Mar 2010 2:43 PM EST
  I experienced peripheral neuropathy for approx. 12 yrs. before being diagnosed with DM2. Vit B12 supplementation has helped tremendously. I... [more]
• Metformin and B12 Deficiency
  Dr. K S S BHAT, 1 Mar 2010 2:43 PM EST
  A good prospective analysis.while Metformin is a very useful drug-esp in cardioDiabetics,in pts particulaly those with s&s of Periph.neuropathy,B12 estimation... [more]
• B12 deficiency and metformin
  Erik L. Johnson, MD, 2 Mar 2010 1:52 PM EST
  I agree with Dr. Joseph: Everybody should already know this. I always gave B12 supplementation and tested my patients. AND... [more]
• Metformin and cobalamin
  Arvind M Jha, Nil, 16 Mar 2010 1:00 PM EST
  Since 1971, it is known that metformin adversely affects cobalamin levels.
  
  However, it is still considered to be a benign... [more]

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