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  Table of Contents     
Year : 2014  |  Volume : 60  |  Issue : 1  |  Page : 95-96

Authors' reply

Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India

Date of Web Publication14-Mar-2014

Correspondence Address:
A K Singh
Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Singh A K, Kumar A, Karmakar D, Jha R K. Authors' reply. J Postgrad Med 2014;60:95-6

How to cite this URL:
Singh A K, Kumar A, Karmakar D, Jha R K. Authors' reply. J Postgrad Med [serial online] 2014 [cited 2023 Jun 2];60:95-6. Available from:


We appreciate the rapid response to our article. [1] A point by point response is outlined below.

  1. The power calculation was based on previous studies done by Reinstatler et al., [2] Liu et al., [3] and Wile et al. [4] Our outcome variable for power calculation defined B 12 deficiency as B 12 level < 220 pg/ml, as has been done by most of these studies.. The values are 16.2, [2] 52, [3] and 31% [4] respectively in the metformin arms of these studies. We thus chose a middle value of expected vitamin B 12 level deficiency percentage to be 25%. Even in the study [1] quoted by the reader, 16.2% of the patients using metformin had borderline B 12 deficiency < 220 pg/ml, while 5.8% (quoted in the abstract of the study by the reader [1] had severe B 12 deficiency (B 12 < 148 pg/ml). In our clinical setting and indeed in most of the studies around the world, a B 12 level of between 200 - 220 pg/ml has been used as a marker of B 12 deficiency. In our study, possible B 12 deficiency and severe deficiency were seen in 21.4% and 7.1% of the patients, respectively. This proportion of B 12 deficiency observed in our study was in agreement with studies across the world, including the National Health and Nutrition Examination Survey (NHANES) [2] referenced by the reader [1] and us, where this figure is 16.8 and 5.8%, respectively. Based on the studies [2],[3],[4] referenced above, we believe that valid assumptions for power calculation were made in our study leading to an appropriate sample size.
  2. Even in the metformin-taking group in our study, 71.5% patients had normal vitamin B 12 levels. Only 21.4% had possible B 12 deficiency and 5.7% had severe B 12 deficiency. As a majority of this group population had above-normal B 12 levels, the mean B 12 level was normal despite this group having a higher proportion of patients with B 12 deficiency than the non-metformin group. The mean level of B 12 in non-vegetarians was higher than vegetarians. Please refer erratum on page (92). Thus, "Vitamin B 12 levels were significantly higher in the non-vegetarian population than in the vegetarian population (529.7 ± 162.3 versus 450 ± 170, p = 0.048, 95% CI 4.41-164.75)." The chi-square test was used to compare the proportion of -vegetarians and not the absolute numbers, as inferred by the reader. [1] As the metformin group had a higher number of patients (n = 84) than the non-metformin group (n = 52), therefore, despite having a higher number of -vegetarians (12 versus 6), the difference in proportion was statistically insignificant (12/84 versus 6/52, difference = 8.30%, 95% CI = -1.59 to 18.19, chi-square = 1.477, p = 0.2243).
  3. Low B 12 levels were observed in all patients with neuropathy. There was negative correlation between the B 12 levels and neuropathy scores. As a majority of the patients in the metformin group had normal B 12 levels, the mean B 12 levels in this group was normal despite having a higher proportion of B 12 deficiency. Thus, a higher proportion of patients with B 12 deficiency in the metformin group accounts for a higher proportion of neuropathy observed in this group, as compared to the non-metformin group.
  4. As has rightly been pointed out by the reader, [1] further studies should be done to evaluate which modes of B12 supplements (intramuscular or oral) are suitable to correct this deficiency.

 :: References Top

1.Shah V. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients. Jr Postgrad Med 2014;60:95.  Back to cited text no. 1
2.Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: The national health and nutrition examination survey, 1999-2006. Diabetes Care 2012;35:327-33.  Back to cited text no. 2
3.Liu KW, Dai DL, Ho W, Lau E, Woo J. Metformin-associated vitamin B12 deficiency in the elderly. Asian J Gerontol Geriatr 2011;6:82-7.  Back to cited text no. 3
4.Wile DJ, Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care 2010;33:156-61.  Back to cited text no. 4


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2004 - Journal of Postgraduate Medicine
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