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K. W. Liu et al.
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The Author 2006. Published by Oxford University Press on behalf of the British Geriatrics Society.
All rights reserved. For Permissions, please email: Metformin-related vitamin B12 deficiency
Medical and Geriatric Unit, Shatin Hospital, New Territories, Hong Kong, China Address correspondence to: Kin Wah Liu. Email: Abstract
Metformin is an invaluable hypoglycaemic agent. We report two cases who had symptomatic vitamin B12 deficiency relatedto metformin use; the mechanisms are discussed. The clinician must be aware of the possibility of metformin-associated B12deficiency in users who suffer cognitive impairment, peripheral neuropathy, subacute combined degeneration of the cord oranaemia.
Keywords: Metformin, elderly, Vitamin B12 deficiency Introduction
Case report 1
The UK Prospective Diabetes Study Group 34 showed An 82-year-old Asian non-vegetarian had type 2 diabetes metformin to be an effective hypoglycaemic agent with mellitus for 20 years. Medications included metformin 1 g less weight gain, and decreased hypoglycaemia, myocar- BD for many years and famotidine for gastritis. She pre- dial infarction, stroke and death [1]. Gastrointestinal sented with memory loss and progressive leg weakness.
side-effects and lactic acidosis related to metformin are Her legs were hypotonic with decreased power, absent commonly recognised; however, the associated vitamin reflexes and bilateral extensor plantar reflexes. Vibration B12 deficiency is less well known. Two cases illustrate and proprioception sense were impaired. The gait was ataxic with a positive Romberg’s test. Mini mental state Metformin-related vitamin B12 deficiency
examination (MMSE) was 9/30. Her haemogloblin level dependent membrane action. The resulting B12 deficiency was 10.3 g/dl with mean corpuscular volume (MCV) 99.7 fl.
can be reversed by administering calcium [7], and this seems Vitamin B12 level was 97 pmol/l with normal folate level and negative anti-intrinsic factor antibodies. Vitamin B12- Diabetes is associated with neuropathy, cognitive deficient subacute combined degeneration of cord and cog- impairment, several causes of anaemia and is on everyone’s nitive impairment related to metformin was suspected.
list of causes of absent ankle reflexes with upgoing plantars; Metformin was stopped, diabetes was stabilised on sulfony- however, it is vital to consider co-existent B12 deficiency, lurea and insulin, and she was given vitamin B12 1000 μg on alternate days for five doses followed by vitamin B12 The value of routine screening for B12 deficiency 1000 μg on a monthly basis. This led to improvements in (recommended by some [5]) is unknown, but the clini- gait, lower limb power, MMSE (20/30) and haematological cian must be aware of this association. The optimum management of such patients is uncertain; although Case report 2
some withdraw metformin and fully investigate thepatient, others take a more pragmatic approach to con- A non-vegetarian diabetic patient had taken over the coun- tinue the metformin, a valuable drug which may not be ter metformin for 8 years, with diarrhoea for 2 years. Her the cause of the deficiency, and to replace the B12 with haemoglobin level was 9.4 g/dl (MCV 104 fl) and B12 level was 125 pmol/l. Anti-parietal cell and anti-intrinsic factorantibodies were negative. Upper gastrointestinal endoscopy and small bowel enema were normal. Schilling test showedintestinal malabsorption. The diarrhoea and haematological Key point
abnormalities resolved on stopping the metformin and • The clinician must be aware of the possibility of metformin- replacing the B12 in the similar manner as patient in case related B12 deficiency in diabetic older patients and test Discussion
These two patients had B12 deficiency associated with References
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depending on population studied and B12 cut-off used.
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diet, gastrointestinal pathology, autoimmune disease and deficiency in elderly patients. CMAJ 2004; 171: 251–9.
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Several studies have screened outpatients taking bigua- absorption of vitamin B12 and intrinsic factor secretion during nides for B12 deficiency. Thirty per cent of 46 patients biguanide therapy. Diabetologia 1983; 24: 16–8.
undergoing biguanide therapy developed B12 malabsorp- 4. Tomkin GH, Hadden DR, Weaver JA et al. Vitamin-B12 status
tion, which resolved in half on stopping the drug [3]. In 71 of patients on long term meformin therapy. BMJ 1971; 2: 685–7.
metformin patients, 21 had low B12 absorption, and four 5. Filioussi K, Bonvoas S, Katsaros T. Should we screen diabetes
had low B12 levels [4]. Fifty-four of 600 patients on long- patients using biguanides for megaloblastic anaemia? AustFam Physician 2004; 32: 383–4.
term biguanides had B12-related megaloblastic anaemia [5].
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What is the mechanism?
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Diabetic people may have slow intestinal transit causing 7. Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V.
bacterial overgrowth and B12 malabsorption; however, Increased intake of calcium reverses vitamin B12 malabsorp- metformin does not alter oral–caecal transit time [6], and tion induced by metformin. Diabetes Care 2000; 23: 1227–31.
there was no evidence of bacterial overgrowth related tometformin in a controlled trial [7]. The B12-intrinsic factorcomplex uptake by ileal cell membrane receptors is known Received 14 March 2004; accepted in revised form 6 December to be calcium-dependent, and metformin affects calcium-



F.E. Wells, D.I. Walker and D.S. Jones (eds) 2003. The Marine Flora and Fauna of Dampier, Western Australia. Western Australian Museum, Perth. Feeding ecology of common intertidal Muricidae (Mollusca: Neogastropoda) from the Burrup Peninsula, Western Australia Tan Koh-Siang Abstract – Indo-Pacific and Australian endemic muricid gastropods form a conspicuous component of the inte

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W0117-Section I (31-50).qxd 4/23/04 7:26 PM Page 124 Polyphagia Ellen N. Behrend P olyphagia is the consumption of food in excess of and liver disease) lead to polyphagia by unknown mecha-normal caloric intake. Hunger and satiety and, conse-nisms. Secondary polyphagia can also be caused by certainquently, feeding behavior are primarily controlled bycertain regions in the central nervous s

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