Metformin Use and Vitamin B12 Deficiency: Untangling the Association

Rodríguez-Gutiérrez, René; Montes-Villarreal, Juan; Rodríguez-Velver, Karla Victoria; González-Velázquez, Camilo; Salcido‐Montenegro, Alejandro; Elizondo-Plazas, Anasofia; González-González, José Gerardo

doi:10.1016/j.amjms.2017.04.010

Cited by 20 publications

(35 citation statements)

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“…While most studies, including meta-analysis reviews, agree that there is an association between vitamin B12 deficiency and the intake of metformin in T2DM patients, a small number of studies have disputed this relationship. 4,5,15,16 The current study confirmed the association between a high metformin dose and vitamin B12 deficiency as concluded by previous studies. 3,10 Patients were found to be at a higher risk of developing vitamin B12 deficiency if they took a larger dose of metformin (>2000 mg/day) and for a longer duration (>4 years).…”

Section: Discussionsupporting

confidence: 91%

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

Al-Hamdi

Al-Gahhafi

Al-Roshdi

et al. 2020

Sultan Qaboos Univ Med J

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Objectives: This study aimed to determine the prevalence of vitamin B12 deficiency amongst diabetic patients on metformin therapy. Methods: This cross-sectional study was conducted at general clinics at the University Health Center and diabetes outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January and December 2017. All Omani adults who were diagnosed with type 2 diabetes mellitus and took metformin were invited to participate in the study. The variables included in this study were age, gender, duration of diabetes, dose and duration of metformin therapy, haemoglobin and glycosylated haemoglobin level. Results: A total of 248 subjects were included (response rate = 95.4%) of which 26 (10.5%) were vitamin B12 deficient and 53 (21.4%) were borderline deficient. The mean daily dose of metformin was highest among vitamin B12 deficient group (1,981 ± 222 mg; P = 0.004). Conclusion: The prevalence of vitamin B12 deficiency is considerable among diabetic patients on metformin therapy. Further research is needed to confirm the need for routine screening and monitoring.Keywords: Type 2 Diabetes Mellitus; Prevalence; Metformin; Vitamin B12 Deficiency; Oman.

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Section: Discussionsupporting

confidence: 91%

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

Al-Hamdi

Al-Gahhafi

Al-Roshdi

et al. 2020

Sultan Qaboos Univ Med J

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“…In Metaxas et al, study [20], Vitamin B12 deficiency was considered to be below 200 ng/mL based on which a frequency of 34% was reported. Also, the relationship between Vitamin B12 serum level and metformin has been demonstrated formerly [21] which is in line with findings of present study.…”

Section: Discussionsupporting

confidence: 92%

An Investigation on Vitamin B12 Serum Levels among Type 2 Diabetic Patients Treated with Metformin Compared to Normal Levels

Samadanifard

Eskandari

Khodabandehloo

et al. 2020

JPRI

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Background: Given the increasing prevalence of type 2 diabetes in the community and the use of metformin as one of its most common therapies as well as presence of some evidences on a link between the use of this medicine and vitamin B12 levels, we decided to measure and compare serum level of vitamin B12 among the diabetic patients under treatment by metformin and compare with its natural content. Decreased Vitamin B12 levels leads to some clinical problems including anemia, gastrointestinal disorders (diarrhea, constipation, decreased appetite, etc.,), neurological disorders (tingle, numbness, muscle weakness, etc.,) and mental disorders (memory impairment, depression, behavioral problems, etc.,). Therefore, we would determine if the duration of metformin use and dosage may be effective on serum levels of vitamin B12 among metformin-treated diabetic patients. Methods: Serum vitamin B12 level in metformin-treated type 2 diabetic patients referred to Rasoul-e-Akram Hospital and Specialist Clinic of Taban in Tehran in 2016 (306 subjects selected by convenience sampling) was determined and then compared to its normal level. Results: Of the 306 participants in the study, 120 ones were females (39.2%) and 186 ones were males (60.8%). Also, 150 ones (49%) were healthy and 156 ones (51%) were suffering from diabetes Miletus. There was a significant difference between the type 2 diabetes mellitus and healthy individuals with quantitative variables such as age, height, weight, BMI, serum cholesterol (Chol) level, LDL serum level, HDL serum level, triglyceride (TG) level. The mean blood level of Vitamin B12 level was 448.92±156.75pg/mL among all participants. A Vitamin B12 deficiency frequency of above 6% was seen among diabetic patients. In regression analysis, a model was defined based on which age, gender, diabetes and Metformin used had a significant effect on serum levels of vitamin B-12. Also, none of the variables gender, age, duration of treatment, metformin quantity, weight and BMI was associated with a deficiency of vitamin B12. Conclusion: In the diabetic group, the prevalence of Vitamin B12 deficiency was more than6%. It was also seen that age, gender, diabetes mellitus, metformin intake and metformin content had a significant effect on serum B12 levels. Therefore, measurement of serum levels of vitamin B12 in metformin-treated subjects is recommended.

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“…Diabetes is a chronic metabolic disorder with various systemic vascular complications, and is one of the leading causes of mortality and morbidity worldwide . Metformin, an oral antihyperglycemic agent, is the first‐line therapy for the treatment of type 2 diabetes (T2D) and is currently the most widely prescribed oral antidiabetic medication …”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have reported associations between metformin use and lower vitamin B 12 levels and/or a higher prevalence of vitamin B 12 deficiency, although a few studies have not found any such association . It has also been reported that the risk of vitamin B 12 deficiency increases with longer duration and/or higher dose of metformin use .…”

Section: Introductionmentioning

confidence: 99%

Associations between metformin use and vitamin B₁₂ levels, anemia, and neuropathy in patients with diabetes: a meta‐analysis

Yang

Cai

Wu³

et al. 2019

Journal of Diabetes

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Highlights• This meta-analysis found that metformin use was associated with a significantly increased risk of vitamin B 12 deficiency and significantly lower serum vitamin B 12 concentrations in a dose-and duration-dependent manner in patients with diabetes. • The meta-analysis did not find significant associations between metformin use and the risk of anemia or neuropathy in patients with diabetes. • Annual vitamin B 12 assessment in diabetic patients taking metformin is recommended, and appropriate preventative and therapeutic measures should be taken when necessary. AbstractBackground: Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B 12 concentrations, which could have hematological or neurological implications. This meta-analyses reviewed all available studies on associations between metformin use and vitamin B 12 levels, anemia, and neuropathy in diabetic patients. Methods: PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes.Results: Thirty-one studies were included in the meta-analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B 12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I 2 = 64%) and significantly lower serum vitamin B 12 concentrations (MD −63.70; 95% CI −74.35, −53.05] pM; P < 0.00001; I 2 = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B 12 concentrations from baseline in diabetic patients (MD −14.68%; 95% CI −17.98%, −11.39%; P < 0.00001; I 2 = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy.Conclusions: Metformin use led to significantly lowered vitamin B 12 concentrations and significantly higher risk of vitamin B 12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use

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Metformin Use and Vitamin B12 Deficiency: Untangling the Association

Cited by 20 publications

References 20 publications

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

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

An Investigation on Vitamin B12 Serum Levels among Type 2 Diabetic Patients Treated with Metformin Compared to Normal Levels

Associations between metformin use and vitamin B₁₂ levels, anemia, and neuropathy in patients with diabetes: a meta‐analysis

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Metformin Use and Vitamin B12 Deficiency: Untangling the Association

Cited by 20 publications

References 20 publications

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

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

An Investigation on Vitamin B12 Serum Levels among Type 2 Diabetic Patients Treated with Metformin Compared to Normal Levels

Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta‐analysis

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Associations between metformin use and vitamin B₁₂ levels, anemia, and neuropathy in patients with diabetes: a meta‐analysis