Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study

Abstract

Aim To assess the vitamin B12 status of patients with type 2diabetes who had been receiving metformin treatment for at least one year. Methods Patients with type 2 diabetes attending a diabetes clinic were included in a cross-sectional cohort study. Patients exposed to metformin for more than one year (n=53) were compared with a non-exposed control group (n=31). Serum cobalamin and other variables reflecting vitamin B12 status were measured. Results Patients on metformin had lower cobalamin (289±137 vs. 395±162 pmol/L; p<0.01) and holotranscobalamin (76±49 vs. 97±41 pmol/L; p<0.05), and higher HCy (11.3+3.3 vs. 10.3±2.3 µmol/L; p<0.05); these changes were correlated. Eight metformin patients, but no controls, had holotranscobalamin below the normal range (p<0.05). Methylmalonic acid and folate were similar in both groups. Conclusion Patients exposed to long-term metformin therapy had 26.7% lower cobalamin, 21.6% lower holotranscobalamin and 9.7% higher HCy serum concentrations than control subjects. Such changes indicate a potential risk for development of vitamin B12 deficiency. Our results highlight the necessity of checking B12 status during metformin therapy.

Vitamin B12 deficiency among adult diabetic patients in Uganda: relation to glycaemic control and haemoglobin concentration

“…Varied prevalence of vitamin B12 deficiency in adult individuals with diabetes has been described by studies performed in different countries outside Africa [2–4, 6, 11–13]. In comparison to the findings in our study, higher frequencies of vitamin B12 deficiency have been reported in U.S. and European studies.…”

“…A cross sectional study by Pflipsen et al involving 203 outpatient type 2 diabetic patients at a large military primary care clinic in USA documented a prevalence of definite vitamin B12 deficiency of 22 % [2]. Similar studies done in Europe have reported prevalence of about 27 % [12, 13]. …”

“…Other studies have demonstrated a close association between vitamin B 12 deficiency and long term use and high dose metformin therapy [3–6, 11, 13, 23]. Metformin has been shown to reduce calcium bioavailability which affects ileal vitamin B12 absorption [1, 24].…”

A review of methods used in assessing non-serious adverse drug events in observational studies among type 2 diabetes mellitus patients

“…In two studies (3%), no inclusion or exclusion criteria were specified [29,30]. Thirteen studies (19%) limited inclusion of patients to lower risk patients (category A) by including only patients with less severe diabetes [20,26,27,31-33] or patients on monotherapy [19,24,27,33-36], or OAD-naïve patients [27,35] or by excluding high risk patients who failed previous therapy [37] or with multiple comorbidity [20,38,39]. Fifteen studies (22%) limited the inclusion to more complicated cases (category B), such as inadequately controlled by or not tolerating previous medication [40-45], receiving combination treatment [46-48] or insulin [21,23,45,49] or treated with maximum dose of medication [50].…”

“…Fifteen studies (22%) limited the inclusion to more complicated cases (category B), such as inadequately controlled by or not tolerating previous medication [40-45], receiving combination treatment [46-48] or insulin [21,23,45,49] or treated with maximum dose of medication [50]. Furthermore, 18 studies (27%) excluded patients based on the presence at baseline of the outcome or a condition that could influence the outcome [18,24,25,33,37-39,47,51-55], non-availability of measurements and/or clinical visits [35,37,46,47,50,54,56,57], inability to fill in questionnaires (category C) [18,21,46,56]. …”