Metformin and Vit B12

[Guest guest]

http://www.medscape.com/viewarticle/545792?sssdmh=dm1.218400 & src=nldne

A nested case-control study published in the October 9 issue of the Archives of

Internal Medicine identified risk factors for vitamin B12 deficiency in patients

with diabetes treated with metformin.

" Identification of risk factors for metformin-related vitamin B12 deficiency has

major potential implications regarding the management of diabetes mellitus, "

write Rose Zhao-Wei Ting, MBBS, from Prince of Wales Hospital, The Chinese

University of Hong Kong in Sha Tin, and colleagues. " First, there is likely to

be an improved yield of detecting vitamin B12 deficiency if high-risk

individuals can be identified. Second, subjects identified as having substantial

risk for metformin-related vitamin B12 deficiency might benefit from empirical

screening or primary prevention with other means such as calcium

supplementation. "

The source population for this nested case-control study was a database that

consisted of subjects who had levels of both serum vitamin B12 and hemoglobin

A1c and were checked in a central laboratory. The investigators identified 155

cases of diabetes mellitus and vitamin B12 deficiency secondary to metformin

treatment, as well as 310 controls who did not have vitamin B12 deficiency while

taking metformin.

In the patients with metformin-related vitamin B12 deficiency, mean serum

vitamin B12 concentration was 148.6 ± 40.4 pg/mL (110 ± 30 pmol/L) compared with

466.1 ± 330.4 pg/mL (344 ± 244 pmol/L) in the controls. After adjustment for

confounders, there were clinically important and statistically significant

associations of vitamin B12 deficiency with dose and duration of metformin use.

Each 1-g/day increment in metformin dose conferred an odds ratio of 2.88 (95%

confidence interval [CI], 2.15 - 3.87) of developing vitamin B12 deficiency (P <

..001).

Compared with those receiving metformin for less than 3 years, the adjusted odds

ratio was 2.39 (95% CI, 1.46 - 3.91) for those using metformin for 3 years or

more (P = .001). After excluding 113 subjects with borderline vitamin B12

concentration, the metformin dose remained the strongest independent predictor

of vitamin B12 deficiency.

" Our results indicate an increased risk of vitamin B12 deficiency associated

with current dose and duration of metformin use despite adjustment for many

potential confounders, " the authors write. " The risk factors identified have

implications for planning screening or prevention strategies in

metformin-treated patients. "

Study limitations include the inability to determine the mechanism of

metformin-related vitamin B12 deficiency; imprecise hospital-based medication

records; possible misclassification of exposure status; lack of matching other

than the date of blood sampling; the use of serum vitamin B12 concentration

alone to define vitamin B12 deficiency; retrospective nature of information

retrieval; unblinded data acquisition method; and inability to determine the

incidence of vitamin B12 deficiency with metformin use.

" We believe our findings should reinforce the heightened vigilance about vitamin

B12 deficiency, " the authors conclude. " Enough concerns exist to call attention

to the value of vitamin B12 screening, particularly among at-risk patients

receiving metformin. Our data underscore the need for monitoring subjects

undergoing high-dose and/or prolonged-course metformin therapy. "

The authors have disclosed no relevant financial relationships.

Arch Intern Med. 2006;166:1975-1979.

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

a.. Describe the benefits of metformin.

b.. Identify risk factors for metformin-related vitamin B12 deficiency.

Clinical Context

Metformin has greatly made an impact on the clinical course and prognosis in

patients with diabetes. The United Kingdom Prospective Diabetes Study confirmed

the long-term benefits of metformin in decreasing diabetes-related end points,

diabetes-related death, and all-cause mortality in overweight patients with

diabetes. Compared with insulin and sulfonylureas, metformin causes less weight

gain and fewer hypoglycemic episodes. Despite all of metformin's benefits,

adverse events may occur. Studies have demonstrated a prevalence of vitamin B12

malabsorption among patients undergoing long-term metformin treatment. The aim

of the current study is to identify risk factors for metformin-related vitamin

B12 deficiency.

Study Highlights

a.. Between January 2003 and November 2005, this case-control study identified

155 cases of diabetes mellitus with vitamin B12 deficiency secondary to

metformin treatment, and 310 controls that did not have vitamin B12 deficiency

while taking metformin.

b.. There were more vegetarians among the control cases; otherwise, no other

significant differences were observed between the 2 groups.

c.. Vitamin B12 deficiency was defined by assay levels of 203.3 pg/mL or less

(? 150 pmol/L).

d.. Patients with metformin-related vitamin B12 deficiency had serum vitamin

B12 concentrations of 148.6 ± 40.4 pg/mL (110 ± 30 pmol/L), and matched controls

had concentrations of 466.1 ± 330.4 pg/mL (344 ± 244 pmol/L).

e.. After adjusting for confounders, results showed clinically important and

statistically significant association of vitamin B12 deficiency with dose and

duration of metformin use.

f.. Each 1-g/day increment of metformin dose conferred a more than 2-fold

increased risk (adjusted odds ratio, 2.88; 95% CI, 2.15 - 3.87) of developing

vitamin B12 deficiency (P < .001).

g.. Among those using metformin for 3 years or more, the adjusted odds ratio

was 2.39 (95% CI, 1.46 - 3.91; P = .001) vs those receiving metformin for less

than 3 years.

h.. After exclusion of 113 subjects with borderline vitamin B12 concentration,

dose of metformin remained the strongest independent predictor of vitamin B12

deficiency.

i.. Limitations to this study included the use of serum vitamin B12

concentration alone to define vitamin B12 deficiency rather than including

metabolites (plasma homocysteine or methylmalonic acid), and the biases of the

study were due to the retrospective and unblinded methods used.

Check Nutrition at my site:

Nutrition.teach-nology.com

Ortiz, RD

nrord@...

" It's what you learn after you know it all that counts. "

~ Harry S. Truman ~