Diabetes
Evaluation of Vitamin B12 Monitoring in a Veteran Population on
Long-Term, High-Dose Metformin Therapy
Sarah A Pierce, Amy H Chung, and Karen Korch Black
etformin, a first-line agent for the
M treatment of type 2 diabetes melli-
tus, has been shown to cause vitamin B12
malabsorption and deficiency.1,2 Serum
vitamin B12 levels have been shown to
be inversely correlated with dose and du-
ration of metformin therapy, and this de-
crease in vitamin B12 level has been
shown to persist and worsen.1,3 This effect
may be due to impairment of the calcium-
dependent ileal absorption of the intrinsic
factor-vitamin B12 complex by met-
formin.3,4 Studies suggest that 10-30% of
patients on long-term metformin therapy
experience vitamin B12 malabsorption,
while 6-9% of patients develop a vitamin
B12 deficiency.5-7 High-dose (2000-2550
mg/day) and long-term (3 or more years)
metformin therapy are the greatest risk
factors for metformin-induced vitamin
B12 deficiency.3 For those on metformin
therapy, the related vitamin B12 deficiency
can take up to 10-15 years to develop.8,9
Because metformin has been on the
American market for over 15 years, the
prevalence of metformin-induced vitamin
B12 deficiency may increase significantly. 9
To detect a vitamin B12 deficiency,
serum vitamin B12 levels are usually ob-
tained. However, the use of serum vitamin
B12 levels alone to diagnose a vitamin B12
deficiency may not be as accurate as the
use of other biomarkers and may lead to
missed diagnoses.10,11 For patients with a subclinical vitamin
B12 deficiency, obtaining a methylmalonic acid and/or homo-
Author information provided at end of text.
1470 n The Annals of Pharmacotherapy
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BACKGROUND: Metformin can result in vitamin B12 deficiency, potentially leading to
complications such as neuropathy. Annual monitoring of vitamin B12 has been
suggested; however, it is unknown whether current practice reflects this recom-
mendation.
OBJECTIVE: To identify vitamin B12 monitoring patterns in patients on long-term, high-
dose metformin. Secondary objective was to determine the frequency of new
vitamin B12 deficiency, anemia, and neuropathy documented after initiation of high-
dose metformin.
METHODS: Electronic medical records of veterans treated at the Veterans Affairs
Maryland Healthcare System with high-dose metformin (≥2000 mg/day) as of
November 1, 2010, were reviewed. Data regarding metformin treatment, vitamin B12
measurements, and documentation of vitamin B12 deficiency, cyanocobalamin
supplementation, anemia, and neuropathy were collected. Subjects treated with
metformin for less than 1 year or those with documented peripheral neuropathy,
megaloblastic anemia, vitamin B12 deficiency, or a condition associated with vitamin
B12 malabsorption prior to metformin initiation were excluded.
RESULTS: Subjects (N = 235) had a mean metformin dose of 2050 mg/day and
mean duration of treatment of 5.2 years. Sixty percent did not have vitamin B12
measured. Of subjects receiving metformin for 10 years or more, nearly half (46%)
never had vitamin B12 measured. New documentation of vitamin B12 deficiency or
cyanocobalamin supplementation was found in 5.5% of the population, and anemia
was found in 12%. Of the 14% with new neuropathy, 42% did not have vitamin B12
measured.
CONCLUSIONS: Vitamin B12 was not routinely monitored in patients on high-dose
metformin, even in those at highest risk (≥10 years of therapy), or in those with
potential manifestations of vitamin B12 deficiency (neuropathy). Cases of vitamin
B12 deficiency and resulting anemia or neuropathy may be undiagnosed and
untreated because of lack of monitoring. Prospective studies examining the effect
of increased vitamin B12 monitoring on identification and treatment of vitamin B12
deficiency in patients on metformin are warranted.
KEY WORDS: diabetes, metformin, monitoring, neuropathy, vitamin B12 deficiency.
Ann Pharmacother 2012;46:1470-6.
Published Online, 31 Oct 2012, theannals.com, doi: 10.1345/aph.1R223
cysteine level can help determine whether a patient has a
clinically significant vitamin B12 deficiency. If either or both
parameters are elevated, the patient can be considered to have
a clinically significant vitamin B12 deficiency and is a candi-
date for cyanocobalamin supplementation.11,12
n 2012 November, Volume 46 theannals.com
 It is important to thoroughly monitor for vitamin B12 de-
ficiency in patients on metformin, as the effects of such a de-
ficiency can be clinically significant in the diabetic popula-
tion. Vitamin B12 deficiency can lead to altered mental status,
megaloblastic anemia, and neurologic damage that often first
presents as peripheral neuropathy.1,9,13 In diabetic patients
treated with metformin, peripheral neuropathy as a result of
an induced vitamin B12 deficiency may be mistaken for dia-
betic neuropathy.9 The progression of neurologic damage due
to vitamin B12 deficiency can be halted by oral or parenteral
cobalamin supplementation.14 However, if the vitamin
B12–mediated neuropathy is misdiagnosed as diabetic neu-
ropathy and the vitamin deficiency goes untreated, perma-
nent neurologic damage can occur.13,15
Routine monitoring of vitamin B12 in diabetic patients
on long-term metformin therapy allows for detection and
correction of low serum concentrations, preventing unneces-
sary hematologic and neurologic complications. Annual
monitoring of hematologic parameters, including serum vita-
min B12 concentrations, has been suggested for patients on
metformin.5-7,9 However, it is unknown how vigilantly mark-
ers of vitamin B12 deficiency are being monitored in this pa-
tient population. The purpose of this study was to evaluate
monitoring of vitamin B12 levels in metformin-treated pa-
tients at the Veterans Affairs Maryland Healthcare System
(VAMHCS), a multifacility network of medical centers and
clinics with a total of 754 beds and 7 outpatient clinics that
serves over 50,000 veterans in Maryland. The primary objec-
tive of this study was to identify serum vitamin B12 monitor-
ing patterns in patients on long-term, high-dose metformin
therapy. The secondary objective was to determine the fre-
quency of complications associated with metformin-induced
vitamin B12 malabsorption, specifically clinical or subclinical
vitamin B12 deficiency, anemia, and neuropathy newly docu-
mented after initiation of high-dose metformin.
Methods
The University of Maryland School of Medicine Institu-
tional Review Board and the VAMHCS Research and Devel-
opment Committee approved this study. Eligible patients had
a diagnosis of type 2 diabetes mellitus and an active prescrip-
tion for high-dose metformin as of November 1, 2010. Pa-
tients were excluded if they had been receiving high-dose
metformin for less than 1 year; had documented vitamin B12
deficiency, megaloblastic anemia, or peripheral neuropathy
prior to high-dose metformin initiation; or had a history of
pernicious anemia, atrophic gastritis, gastrointestinal surgery
(ileal resection, partial or complete gastrectomy, or gastric
banding or bypass), celiac sprue, Crohn disease, alcoholism,
chronic pancreatitis, malabsorption syndrome, HIV infection,
or Helicobacter pylori infection documented in the problem
list of their electronic medical record due to the vitamin B12
malabsorption associated with these conditions. For this
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study, high-dose metformin was defined as a dose of at least
2000 mg/day. Long-term metformin therapy was defined as
treatment with high-dose metformin for at least 1 year.
Data were collected from electronic medical records for
each year of high-dose metformin treatment, from the end
of year 1 of therapy to the end of the study period. Year 1 was
defined as the year in which the subject was first prescribed
high-dose metformin. End of study was defined as Novem-
ber 1, 2010. For each subject, the following data were collect-
ed: age; metformin dose; duration of high-dose metformin
treatment; whether there was a new prescription for cyanoco-
balamin during the study period; new documentation of ane-
mia, neuropathy, or vitamin B12 deficiency during the study
period; serum vitamin B12 level; hemoglobin level; mean cor-
puscular volume; and serum methylmalonic acid (MMA)
level. For subjects with multiple laboratory values in a single
year, the highest metformin dose and MMA values and the
lowest serum vitamin B12 and hemoglobin values were
recorded. Descriptive statistics were compiled for patient de-
mographics, vitamin B12 monitoring patterns, and frequency
of vitamin B12 deficiency, anemia, and neuropathy.
Results
Eight hundred sixty-nine patients were identified as hav-
ing an active prescription for high-dose metformin as of
November 1, 2010. Charts of 300 randomized patients
were reviewed for eligibility.16 Sixty-five individuals were
ineligible for the study, with the majority excluded because
of peripheral neuropathy at baseline, alcohol abuse, or du-
ration of metformin therapy of less than 1 year. Demo-
graphics of the 235 included subjects are listed in Table 1.
VITAMIN B12 MONITORING
Vitamin B12 monitoring patterns, stratified by duration of
metformin therapy, are illustrated in Figure 1. Among all sub-
jects included in the study, 60% did not have a serum vitamin
B12 level measured during high-dose metformin treatment. In
addition, among subjects who had been on high-dose met-
formin for the longest time (at least 10 years) and were there-
fore at greatest risk of vitamin B12 deficiency, nearly half
(46%) had never had a vitamin B12 level measured. Less than
1% of subjects had a serum vitamin B12 measured yearly.
Table 1. Demographics
Characteristic Value
Pts., N 235
Age at year 1, mean (SD), years 59 (9.2)
Metformin dose at year 1, mean (range), mg/day 2050 (2000-2550)
Duration of high-dose metformin therapy, mean 5.2 (3.0)
(SD), years
n 2012 November, Volume 46 n 1471
SA Pierce et al.
Among the 62 study subjects with a serum vitamin B12 mea-
surement of less than 350 pg/mL (reference range 157-1059),
77% did not have a follow-up MMA level measured.
INCIDENCE OF VITAMIN B12 DEFICIENCY, ANEMIA, AND
NEUROPATHY
Six (2.5%) subjects had a new vitamin B12 deficiency
documented after a mean of 4.5 years of high-dose met-
formin therapy. However, 13 subjects (5.5%) had a new
prescription for cyanocobalamin supplementation during
the study period (Figure 2). Forty-eight (18%) patients did
not have a new cyanocobalamin prescription or an MMA
Figure 1. Total number of serum vitamin B12 measurements per sub-
ject by duration of high-dose (≥2000 mg/day) metformin therapy.
All subjects: N = 235; ≤3 years: n = 87; 4-6 years: n = 83; 7-9 years: n =
39; ≥10 years: n = 26.
Figure 2. Incidence of new documentation of vitamin B12 deficiency (n = 6), cyanocobalamin use (n = 13), anemia (n = 28), and neuropathy (n = 33)
among included subjects (N = 235) during high-dose metformin therapy.
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level measured despite having a serum vitamin B12 level
less than 350 pg/mL while on metformin. New documen-
tation of anemia and neuropathy was noted in 28 (12%)
and 33 (14%) subjects, respectively. Among these subjects,
29% of those with newly documented anemia and 42% of
those with newly documented neuropathy had no docu-
mentation of serum vitamin B12 measurement (Figure 3).
Discussion
VITAMIN B12 MONITORING
Less than 1% of study subjects met the recommendation
of having a serum vitamin B12 level measured annually
while on high-dose metformin therapy; most never had the
level determined. This finding persisted regardless of the
duration of high-dose metformin therapy. The risk of de-
veloping a metformin-induced vitamin B12 deficiency is
positively correlated with the duration of metformin use.3
Thus, it is notable that among subjects with a duration of
high-dose metformin treatment of 10 years or more, nearly
half (46%) never had a vitamin B12 level measured during
therapy (Figure 1). These individuals were at the greatest
risk for vitamin B12 deficiency, and the lack of monitoring
in these subjects may have resulted in several cases of vita-
min B12 deficiency being undiagnosed and untreated.
As previously discussed, patients with a potential sub-
clinical vitamin B12 deficiency (defined in this study as a vi-
tamin B12 level <350 pg/mL) should have a more sensitive
marker, such as MMA, measured.2,10 In this study, subjects
with low-normal vitamin B12 levels did not routinely have
follow-up MMA levels evaluated. Clinically significant vita-
min B12 deficiencies may have gone undiagnosed and un-
treated resulting from this lack of thorough monitoring.
theannals.com

Lack of awareness may explain the results found in this
study. While monitoring vitamin B12 with metformin may
be novel to some, the relationship between metformin and
vitamin B12 deficiency has been recognized for several
decades, and monitoring vitamin B12 was a recommenda-
tion during the time frame of this retrospective study.5-7
However, while this recommendation is included in readily
available drug information sources, the clinical practice
guidelines from the American Diabetes Association do not
mention the need to monitor vitamin B12. The guidelines
do not include such specific recommendations regarding
monitoring parameters for the medications used to treat di-
abetes. Thus, the lack of vitamin B12 monitoring found in
the study could be because many providers may be unfa-
miliar with this adverse effect of metformin and unaware
of the recommendation to monitor the vitamin.
Given the low rates of vitamin B12 monitoring seen in
this study, it is prudent to note that annual injections of vi-
tamin B12 have been suggested as an alternative to annual
monitoring of vitamin B12 levels in patients on long-term
therapy. This approach may be more cost-effective and
could also be considered, especially if access to primary
care or laboratory services is a concern.9
INCIDENCE OF VITAMIN B12 DEFICIENCY, ANEMIA, AND
NEUROPATHY
Vitamin B12 Deficiency
A new vitamin B12 deficiency was documented in the
charts of 2.5% of subjects after an average of 4.5 years of
metformin therapy. However, 5.5% of subjects had new
prescriptions for cyanocobalamin supplementation, which
suggests that a larger percentage than was documented expe-
rienced a clinically significant decrease in vitamin B12 levels
while on high-dose metformin therapy. The pro-
portion of patients with clinically significant de-
creases in vitamin B12 may have been even
greater, as an additional 18% had a vitamin B12
level less than 350 pg/mL but no follow-up mea-
surement of MMA levels and no prescription for
cyanocobalamin. Thus, when including the 5.5%
of subjects who received cyanocobalamin sup-
plementation and the 18% with a potential sub-
clinical vitamin B12 deficiency, it is possible that
up to 23.5% of patients may have experienced a
clinically significant decrease in vitamin B12 dur-
ing high-dose metformin therapy. These findings
are comparable to those in other studies, which
identified 10-30% of patients on long-term met-
formin therapy as having some degree of vita-
min B12 malabsorption.5-7 The percentage of in-
dividuals in this study who received cyanocobal-
amin supplementation (5.5%) is slightly lower
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Vitamin B12 Monitoring in Patients on Metformin
than the reported rate of vitamin B12 deficiency in patients
on long-term metformin (6-9%).5-7
Anemia
Measuring vitamin B12 and folate levels is often part of a
routine evaluation when a patient is found to have ane-
mia.17 However, 29% of subjects in this study with a new
documentation of anemia during high-dose metformin
therapy did not have a vitamin B12 level measured; an addi-
tional 36% with a vitamin B12 level less than 350 pg/mL
did not have a follow-up MMA level or a cyanocobalamin
prescription documented. Thus, up to 64% of the subjects
on high-dose metformin with anemia may have had a clin-
ically significant vitamin B12 deficiency underlying their
anemia that went undetected.
Neuropathy
Neurologic damage, a possible consequence of met-
formin-induced vitamin B12 deficiency, can present as pe-
ripheral neuropathy and may be mistaken for diabetic neu-
ropathy in patients on high-dose metformin.9 In these pa-
tients, detection of a vitamin B12 deficiency and correction
with cyanocobalamin is a simple means to potentially halt
progression of the neuropathy and prevent permanent neuro-
logic damage. In addition, the findings of Wile and Toth
demonstrated that metformin-treated diabetic patients had
more severe worsening of peripheral neuropathy compared
to diabetic patients with neuropathy who were not on met-
formin.18 In our study, less than one third of subjects with a
new documentation of neuropathy received a comprehensive
workup for vitamin B12 deficiency (Figure 3). Although par-
ticular attention should be paid to monitoring vitamin B12 lev-
els in diabetic patients on metformin who have or develop
neuropathy, the lack of vitamin B12 monitoring seen in the
Figure 3. Vitamin B12 monitoring in subjects with anemia or neuropathy. Proportion
of subjects with new documentation of anemia (n = 28) or neuropathy (n = 33) who
did not have vitamin B12 levels measured at any time and who received an incom-
plete workup for vitamin B12 deficiency (defined as a vitamin B12 level <350 pg/mL
without a follow-up methylmalonic acid level or cyanocobalamin prescription), or who
received a complete workup for vitamin B12 deficiency (defined as a vitamin B12 level
>350 pg/mL, or a vitamin B12 level <350 pg/mL with a follow-up methylmalonic acid
level and/or cyanocobalamin prescription). Anemia: no vitamin B12 measured, n = 8
(29%); incomplete vitamin B12 workup, n = 11 (39%); complete vitamin B12 workup, n
= 9 (32%). Neuropathy: no vitamin B12 measured, n = 14 (42%); incomplete vitamin B12
workup, n = 9 (27%); complete vitamin B12 workup, n = 10 (30%).
The Annals of Pharmacotherapy n 2012 November, Volume 46 n 1473
SA Pierce et al.
overall study population persisted in the subjects with neu-
ropathy, a patient population for whom the consequences of
an untreated vitamin B12 deficiency may be most significant.
STUDY STRENGTHS AND LIMITATIONS
This study has several strengths. Only subjects at high
risk of metformin-induced vitamin B12 deficiency were in-
cluded in the study, as all patients were on high doses for
considerable periods. Thus, the subsequent finding that vi-
tamin B12 was not being adequately monitored has greater
significance given that this lack of monitoring occurred in
a high-risk population. The use of an integrated electronic
medical record that includes medical diagnoses and medi-
cation prescription information allows for more compre-
hensive data collection, and the random sample of patients
included in the study provides a more accurate picture of
actual clinical practice.
This study also fills a gap in the literature. While several
studies demonstrating the relationship between metformin
use and vitamin B12 deficiency support the need for routine
monitoring of serum vitamin B12 levels, there is a lack of
studies that examine whether this monitoring is being per-
formed in the clinical setting. This study adds to the litera-
ture by highlighting the fact that patients on long-term,
high-dose metformin do not routinely have vitamin B12
levels measured, despite mounting evidence in favor of do-
ing so, and potential cases of reversible vitamin B12 defi-
ciencies may therefore go undiagnosed.
The study is not without limitations, however. Due to
the study’s retrospective design, there are inherent limita-
tions to the data. For example, with use of refill records alone,
it was not possible to determine adherence to the prescribed
metformin regimen. In addition, only medical conditions and
medications explicitly recorded in a subject’s medical record
and medication lists were reviewed for inclusion, exclusion,
and data collection. Thus, some patients may have had active
medical conditions that were not documented in their com-
puterized medical records, and therefore the information was
not available. This may have led to an underrepresentation of
the incidence of vitamin B12 deficiency, anemia, and neuropa-
thy in this study. This is evidenced by the fact that while only
6 subjects had a documented vitamin B12 deficiency, 13 pa-
tients had a new prescription for cyanocobalamin supplemen-
tation during the study period.
Because data were obtained only from the electronic
medical records of the VAMHCS, it is possible that sub-
jects may have previously filled prescriptions, including
metformin, outside of the VA system. Therefore these non-
VA medications and durations of use were not documented
during chart review and data collection.
Finally, data were recorded only for the period after sub-
jects had been started on high-dose metformin. They may
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have been receiving a lower dose of metformin, resulting
in a difference between the recorded duration of high-dose
metformin therapy versus the total duration of metformin
therapy at any dose. As such, the cumulative duration of
metformin use at any dose was not captured and could not
be analyzed in reference to the development of vitamin B12
deficiency or related complications. In addition, while all
subjects were on high-dose therapy at the start and end of
the study period, subjects who had temporary dose adjust-
ments to doses <2000 mg/day during the study period were
not excluded and these dose adjustments were not explicit-
ly accounted for in the study. This is a limitation, as these
subjects would technically be at a slightly lower risk dur-
ing the time of lower dose therapy. However, this is unlike-
ly to significantly affect the results, since the purpose of the
study was to evaluate overall vitamin B12 monitoring pat-
terns in a higher-risk group of patients rather than to prove
a dose-dependent relationship between metformin and vi-
tamin B12 levels.
In conclusion, the results of this study demonstrate that
vitamin B12 levels are not being routinely monitored as rec-
ommended in patients on long-term, high-dose metformin
therapy. The discrepancy between recommended and actu-
al practice is possibly caused by a lack of awareness re-
garding the effects of metformin on vitamin B12 absorp-
tion. It is important to educate providers about the utility of
checking a vitamin B12 level annually in patients on long-
term, high-dose metformin therapy, given that measuring a
serum vitamin B12 level is a readily available laboratory
test and the detection and correction of a simple vitamin
B12 deficiency can prevent unnecessary permanent neuro-
logic damage and anemia in this patient population.
Because the vitamin B12– deficient state induced by met-
formin can emerge over the course of 10-15 years, this is-
sue will likely become more clinically significant, consid-
ering that metformin has been on the US market for 16
years. It is possible that the rates of vitamin B12 deficiency
attributed to long-term use of high-dose metformin could
increase substantially. It is imperative that clinicians be
aware of this potentially serious, yet easy-to-treat, adverse
effect of metformin and be proactive in annually monitor-
ing serum vitamin B12 levels in this high-risk population.
Sarah A Pierce PharmD, PGY1 Pharmacy Practice Resident, VA
Maryland Healthcare System— Department of Pharmacy, Baltimore,
MD
Amy H Chung PharmD, Clinical Pharmacy Specialist, VA Mary-
land Healthcare System—Department of Pharmacy
Karen Korch Black PharmD, PGY2 Ambulatory Care Pharmacy
Residency Program Director; Clinical Pharmacy Specialist, VA Mary-
land Healthcare System—Department of Pharmacy
Correspondence: Dr. Pierce, sarah.pierce@va.gov
Reprints/Online Access: www.theannals.com/cgi/reprint/aph.1R223
Conflict of interest: Authors reported none
We thank Christopher Gallagher PharmD for his assistance with this work.
theannals.com

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EXTRACTO
El Seguimiento a las Concentraciones de Vitamina B12 en Una
Población de Veteranos que Utilizan Dosis Altas de Metformin por
Periodos Largos de Tiempo
SA Pierce, AH Chung, y KK Black
Ann Pharmacother 2012;46:1470-6.
TRASFONDO: El uso de metformin puede llevar a deficiencia de vitamina
B12 lo cual puede potencialmente llevar a complicaciones como neuro-
patía. Se ha sugerido que se provea seguimiento anual a las concentraci-
ones de vitamina B12, sin embargo no se conoce si la práctica usual
actual refleja esta recomendación.
OBJETIVO: Identificar los patrones de seguimiento a las concentraciones de
vitamina, B12 en pacientes que utilizan metformin en altas dosis y por largos
periodos de tiempo. Los objetivos secundarios fueron determinar la frecu-
encia de una deficiencia nueva de vitamina B12, de anemia y neuropatía que
hayan sido documentadas luego de iniciar metformin en dosis altas.
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Vitamin B12 Monitoring in Patients on Metformin
MÉTODOS: Se revisaron retrospectivamente los expedientes médicos electró-
nicos de los veteranos que fueron tratados con dosis altas de metformin
(>2000 mg/día) desde el 1 de noviembre de 2010 en el Sistema de Salud
de Veteranos de Maryland. Se recopiló la información relacionada con el
tratamiento de metformin, las medidas de concentraciones de vitamina B12,
y la documentación relacionada con deficiencia de vitamina B12, uso de
suplementos con cianocobalamina, anemia y neuropatía. Se excluyeron del
estudio las personas tratadas con metformin por menos de un año o que
tenían documentado, previo al inicio del tratamiento con metformin, neuro-
patía periferal, anemia megaloblástica, deficiencia de vitamina B12, o la pre-
sencia de condiciones asociadas con problemas de malabsorción de
vitamina B12.
RESULTADOS: Se identificaron 235 personas que utilizaban metformin con
una dosis promedio de 2050 mg/día y tenían un promedio de duración de
tratamiento de 5.2 años. Al 60% de los sujetos en ningún momento se le
tomó medidas de concentraciones de vitamina B12. De los sujetos que
utilizaban metformin por más de 10 años, aproximadamente la mitad
(46%) nunca tuvo una medida de las concentraciones de vitamina B12.
Se encontró que se había documentado por primera vez deficiencia de
vitamina B12 o suplementación con cianocobalamina en 5.5% de los
sujetos y anemia en 12% de los pacientes. Del 14% de los sujetos que
presentaron neuropatía por primera vez, el 42% de los mismos nunca
tuvo medidas de concentración de vitamina B12.
CONCLUSIONES: No se provee seguimiento rutinario a las concentraciones
de vitamina B12 en pacientes que utilizan metformin en dosis altas, aún
en aquellas personas de alto riesgo (>10 años de tratamiento) o que tienen
el potencial de manifestar deficiencia de vitamina B12 (neuropatía). Los
casos de deficiencia de vitamina B12 que resultan en anemia o neuropatía
pudieran estar poco diagnosticados y no ser tratados debido a la falta de
seguimiento. Se necesitan estudios prospectivos que examinen el efecto
de proveer seguimiento a las concentraciones de vitamina B12 en la identi-
ficación y tratamiento de esta deficiencia en pacientes que utilizan met-
formin.
Traducido por Mirza Martínez
RÉSUMÉ
Évaluation de la Surveillance des Taux de Vitamine B12 Chez une
Population d’Anciens Combattants sous Traitement à Long terme de
Metformine en Dose Élevée
SA Pierce, AH Chung, et KK Black
Ann Pharmacother 2012;46:1470-6.
OBJECTIF: Identifier la nature des suivis des taux de vitamine B12 chez les
patients utilisant à long terme des doses élevées de metformine. Les
objectifs secondaires étaient de déterminer la fréquence d’une carence en
vitamine B12, l’anémie et la neuropathie documentées suite à l’instauration
d’une dose élevée de metformine.
MÉTHODES: Au premier novembre 2010, les dossiers médicaux électro-
niques des Anciens Combattants suivis au VA Maryland Healthcare
System ayant des doses élevées de metformine (>2000 mg/jour) ont été
revus de façon rétrospective. Les données sur le traitement au metformine,
les niveaux de vitamine B12, et la documentation de la carence en vita-
mine B12, la supplémentation en cyanocobalamine, l’anémie et la neuro-
pathie ont été recueillies. Les patients traités avec de la metformine pour
une période de moins de 1 an ou avec une documentation de neuropathie
périphérique, une anémie mégaloblastique, une carence en vitamine B12
ou une maladie associée à la malabsorption de la vitamine B12 avant le
début du traitement avec la metformine ont été exclus de l’étude.
RÉSULTATS: Les patients (n = 235) prenaient une dose moyenne de 2050
mg/jour de metformine et une durée de traitement de 5.2 ans. Soixante
pourcent des sujets n’avaient pas de documentation de leur taux de vita-
mine B12. Des patients qui recevaient de la metformine pour plus de 10
ans, presque la moitié (46%) n’avaient jamais eu de détermination du
taux de vitamine B12. Une nouvelle documentation de carence en vita-
mine B12 ou une supplémentation de cyanocobalamine ont été documentées
chez 5.5% des sujets et l’anémie chez 12%. Des 14% des patients avec
une nouvelle neuropathie, 42% n’avaient pas de documentation de taux
de vitamine B12.
CONCLUSIONS: Les taux de vitamine B12 ne sont pas régulièrement
contrôlés chez les patients avec des doses élevées de metformine, même
n 2012 November, Volume 46 n 1475
SA Pierce et al.

si les patients sont à risqué élevés (≥10 ans de traitement) ou avec des
manifestations potentielles (neuropathie) de carence en vitamine B12. Les
patients avec carence en vitamine B12 entraînant une anémie ou une
neuropathie risquent d’être non diagnostiqués ni traités en l’absence de
données de surveillance. Des études prospectives doivent être effectuées
pour évaluer l’effet de la surveillance du taux de la vitamine B12 dans
l’identification et le traitement de carence en vitamine B12 chez les
patients sous metformine.
Traduit par Louise Mallet

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