Should we screen diabetic patients using biguanides for megaloblastic anaemia?

Aust Fam Physician. 2003 May;32(5):383-4.


Background: Patients taking biguanides on a continuous basis sometimes develop vitamin B12 deficient megaloblastic anaemia. The prevalence of this side effect has not been estimated.

Methods: We screened 600 patients with type 2 diabetes treated with biguanides (phenformin or metformin) for a mean of 11.8 years (SD: 3.6 years) with complete blood counts, red cell indices and red cell morphology. If this showed macrocytosis, we measured total serum vitamin B12 and antiparietal cells antibodies (APCA). Patients with macrocytosis and low serum vitamin B12 levels were treated with cyanocobalamin 1 mg injection daily for seven days.

Results: Fifty-four (9%) of the patients had megaloblastic anaemia with low serum total vitamin B12 levels, only three (0.5%) also had abnormally raised APCA. All 54 patients responded to cyanocobalamin with a reticulocyte increase within 10 days.

Conclusion: Annual screening for megaloblastic anaemia in patients on long term treatment with biguanides may be worthwhile. The anaemia is easily remediable and does not necessitate withdrawal of the drug.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Megaloblastic / chemically induced*
  • Anemia, Megaloblastic / diagnosis*
  • Biguanides / adverse effects*
  • Biguanides / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Male
  • Mass Screening / standards*
  • Middle Aged
  • Time Factors


  • Biguanides