Metformin Use and Vitamin B<SUB>12</SUB> Deficiency in Patients with Type-2 Diabetes Mellitus

Abstract

Metformin is commonly used oral hypoglycaemic agent in the treatment of type-2 Diabetes Mellitus (DM). One of the important side effect of long term metformin therapy is malabsorption of vitamin B 12 which could lead to megaloblastic anemia and peripheral neuropathy. Therefore annual screening of serum vitamin B 12 level or serum methylmalonic acid (MMA)/serum homocysteine level should be done in cases taking metformin for more than four to five years with average dose of >1g per day, even in the absence of haematological or neurological abnormalities. However, as the incidence of type-2 DM is increasing, cost of annual measurement of vitamin B 12 level also increases. Considering cost factor for annual screening, vitamin B 12 supplementation appears to be more cost effective approach rather than annual screening for routine prophylaxis. Routine vitamin preparations available in the market may contain less amount of B 12 and hence are not of much therapeutic use in treatment of B 12 deficiency due to Metformin. Hence there is a need to look for higher doses of approximately 500-2000μg/day.

Anemia in Type 2 Diabetes Mellitus (T2dm) and its association with vitamin B12 deficiency

“…15 The principal source of vitamin B12 includes liver, egg yolk, meat, cheese etc. 13 But in our study most (56.5%) of the study population are vegetarian, which can also be the cause of increased number of patients presented with macrocytic anemia.…”

“…However due to storage in liver, clinical symptoms of vitamin B12 deficiency may manifest after 5-10 years. 13 Metformin hydrochloride is a biguanide which lowers both fasting and post-prandial glucose in type 2 diabetics. It acts mainly by improving insulin sensitivity and decreasing hepatic glucose production.…”

Efektivitas Penggunaan Kombinasi Vitamin B pada Pasien Neuropati Diabetikum

“…Penggunaan metformin jangka panjang sering terkait dengan malabsorpsi vitamin B 12 yang menimbulkan defisiensi vitamin B 12 (Fatima & Noor, 2013;Reinstatler dkk., 2012). Defisiensi vitamin B 12 tersebut merupakan salah satu pemicu munculnya neuropati perifer pada pasien DM (Jeetendra & Tushar, 2016), khususnya pada usia ≥ 65 tahun (Zagar & Longyhore, 2014). Oleh karena itu, pasien DM yang memperoleh pengobatan metformin jangka lama (> 6 bulan) disarankan untuk juga memperoleh suplementasi vitamin B 12 untuk mencegah terjadinya ND (Roy dkk., 2016).…”

Assessment of Metformin Induced Vitamin-B12 Deficiency amongst Type-II Diabetic Patients Vis-À-Vis Evaluating the Quality of Life

“…Hence in early stages progression of neurological damage could be managed by early detection of vitamin B12 and this vitamin B12 deficiency may lead to permanent neurological damage if it is misdiagnosed as diabetic neuropathy. 2 In an Indian study conducted among 441 healthy middle-aged men, the vitamin B12 deficiency was observed among 67% of the study participants. 3 Vegetarian concentrations <150 pmol/L where diet was a significant factor associated with low vitamin B12 levels in this study on multivariate analysis.…”

“…Furthermore, because vitamin B12 participates in the most critical pathway of homocysteine (Hcy) metabolism, a reduction in vitamin B12 would increase plasma concentrations of Hcy, which is strongly linked to cardiovascular disease in patients with T2DM and PCOS. (2) The various causes of vitamin B12 deficiency include nutritional deficiency, gastric mucosal damage, pernicious anaemia, drugs like metformin and Proton Pump Inhibitors (PPIs). 1. Hence various mechanisms have been proposed to explain vitamin B12 deficiency observed amongst Type-2 DM patients taking metformin therapy which are: changes in small intestinal motility which stimulates bacterial overgrowth and consumption of B12 by bacteria, changes in Intrinsic Factor (IF) levels which could adversely affect vitamin B12 absorption.…”