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

Abstract

Background 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 2 = 64%) and significantly lower serum vitamin B 12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P 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 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 hig…