The Risk of Cobalamin Deficiency Symptoms Related to Long-Term Metformin Use in T2dm Patients

Abstract

Background. Metformin is the first-line oral antidiabetic agent used in the treatment of diabetes mellitus. One of the adverse reactions of the long term use of metformin is cobalamin malabsorption. Clinical and laboratory findings are important in the diagnosis of cobalamin deficiency.Objective. This study aimed to evaluate the risk of cobalamin deficiency symptoms related to long-term use of metformin in type 2 diabetes mellitus patients at Pasar Rebo General Hospital in Jakarta.Setting. This quantitative, observational study with retrospective cohort design was conducted in outpatient department Pasar Rebo General Hospital November 2015 until January 2016.Methods. 200 subjects were recruited and divided into two groups, patients who had been taking metformin for 1-3 years and patients who had been taking metformin for more than 3 years. Each patient was assessed for the presence of cobalamin deficiency symptoms.Main outcome measure. Cobalamin deficiency symptoms evaluated were symptoms of neuropathy (measured by DN4 questionnaire) and hematologic abnormalities associated to cobalamin deficiency, i.e. macrocytic erythrocyte, hypersegmented neutrophils, and giant bands.Results. There are significant differences in the proportions of neuropathy symptoms (RR 2.36, 95%, p=0.000) and hematologic abnormalities (RR 1.5, 95%, p=0.007) between the two groups.Conclusions. Long-term use of metformin (≥3 years) may increase the risk of cobalamin deficiency symptoms in type 2 diabetes mellitus patients.

Vitamin B12 Deficiency in Diabetic Patients on Metformin Therapy: A cross-sectional study from Oman

“…8 Studies have reported conflicting findings regarding the consequences of vitamin B12 deficiency in T2DM patients. 6,10,11 Hendrawati et al reported higher proportions of neuropathy symptoms and haematologic abnormalities among patients who took metformin for a longer period of time (>3 years versus 1-3 years). 11 Aroda et al 's large cohort study of 2,155 participants found a higher prevalence of neuropathy and anaemia in the metformin group compared to the placebo group.…”

“…6,10,11 Hendrawati et al reported higher proportions of neuropathy symptoms and haematologic abnormalities among patients who took metformin for a longer period of time (>3 years versus 1-3 years). 11 Aroda et al 's large cohort study of 2,155 participants found a higher prevalence of neuropathy and anaemia in the metformin group compared to the placebo group. 6 On the other hand, Alharbi et al 's study found no significant differences in the prevalence of peripheral neuropathy between metformin users and non-metformin users.…”

“…10 In such patients, early detection of vitamin B12 deficiency is important to avoid subsequent haematological and neurological manifestations. 11 While the exact role of vitamin B12 in the pathogenesis of T2DM is still unknown, studies have indicated a possible association between vitamin B12 deficiency and serious diabetic complications such as peripheral neuropathy. 12 It is hypothesised that oxidative stress is the common associated factor in both conditions.…”

Red Cell Distribution Width and Acute Complications of Diabetes

“…Second, investigations of inflammation markers other than CRP such as IL-2 and TNF-α may help to clarify the pathogenesis of the relationship between red blood cell indices and inflammation. Third, we could not evaluate the body mass index of the patients, the history of smoking and the history of metformin usage, due to retrospective design of the study (28,29). These factors could have affected the RDW values.…”

The vitamin B12 levels in type 2 diabetes mellitus patients on metformin and not on metformin

“…22 Proposed mechanisms to explain metformin induced vitamin B12 deficiency among T2DM patients include: alterations in small bowel motility, competitive inhibition or inactivation of vitamin B12 absorption, alterations in intrinsic factor (IF) levels, interaction with the cubulin endocytic receptor and inhibition of calcium dependent absorption of vitamin B12-IF complex at the terminal ileum. [23][24][25]…”