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

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#anemia #case-control-studies #diabetes-mellitus-type-2 #humans #hypoglycemic-agents

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

Yang et al., 2019 | J Diabetes | Meta Analysis

Citation

Yang Wenjia, Cai Xiaoling, ... Ji Linong. Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis. J Diabetes. 2019-Sep;11(9):729-743. doi:10.1111/1753-0407.12900

Abstract

BACKGROUND: Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B12 concentrations, which could have hematological or neurological implications. This meta-analyses reviewed all available studies on associations between metformin use and vitamin B12 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 B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2  = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2  = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD -14.68%; 95% CI -17.98%, -11.39%; P < 0.00001; I2  = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy. CONCLUSIONS: Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B12 assessment in diabetic patients taking metformin is recommended.

Key Findings

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 B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2  = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2  = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population diabetes
Sample Size See abstract
Age Range See abstract
Condition diabetes

MeSH Terms

  • Anemia
  • Case-Control Studies
  • Diabetes Mellitus, Type 2
  • Humans
  • Hypoglycemic Agents
  • Metformin
  • Peripheral Nervous System Diseases
  • Prognosis
  • Vitamin B 12
  • Vitamin B Complex

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis
  • Vertical: vitamin-b12

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09