Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans

J Am Geriatr Soc. 2017 May;65(5):1061-1066. doi: 10.1111/jgs.14761. Epub 2017 Feb 9.


Objective: To examine the association between long-term metformin therapy and serum vitamin B12 monitoring.

Design: Retrospective cohort study.

Setting: A single Veterans Affairs Medical Center (VAMC), 2002-2012.

Participants: Veterans 50 years or older with either type 2 diabetes and long-term metformin therapy (n = 3,687) or without diabetes and no prescription for metformin (n = 13,258).

Measurements: We determined diabetes status from outpatient visits, and defined long-term metformin therapy as a prescription ≥500 mg/d for at least six consecutive months. We estimated the proportion of participants who received a serum B12 test and used multivariable logistic regression, stratified by age, to evaluate the association between metformin use and serum B12 testing.

Results: Only 37% of older adults with diabetes receiving metformin were tested for vitamin B12 status after long-term metformin prescription. The mean B12 concentration was significantly lower in the metformin-exposed group (439.2 pg/dL) compared to those without diabetes (522.4 pg/dL) (P = .0015). About 7% of persons with diabetes receiving metformin were vitamin B12 deficient (<170 pg/dL) compared to 3% of persons without diabetes or metformin use (P = .0001). Depending on their age, metformin users were two to three times more likely not to receive vitamin B12 testing compared to those without metformin exposure, after adjusting for sex, race and ethnicity, body mass index, and number of years treated at the VAMC.

Conclusion: Long-term metformin therapy is significantly associated with lower serum vitamin B12 concentration, yet those at risk are often not monitored for B12 deficiency. Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement.

Keywords: aging; metformin; type 2 diabetes; veterans; vitamin B12.

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Hospitals, Veterans
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Veterans / statistics & numerical data*
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / chemically induced*


  • Hypoglycemic Agents
  • Metformin