Risk of anemia with metformin use in type 2 diabetes: A MASTERMIND study

Louise A. Donnelly, John M. Dennis, Ruth L. Coleman, Naveed Sattar, Andrew T. Hattersley, Rury R. Holman, Ewan R. Pearson (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
221 Downloads (Pure)


Objective: To evaluate the association between metformin use and anemia risk in type 2 diabetes, and the time-course for this, in a randomized controlled trial (RCT) and real-world population data.

Research design and methods: Anemia was defined as a hemoglobin measure of <11 g/dL. In the RCTs A Diabetes Outcome Progression Trial (ADOPT; n = 3,967) and UK Prospective Diabetes Study (UKPDS; n = 1,473), logistic regression was used to model anemia risk and non-linear mixed models for change in hematological parameters. In the observational Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) population (n = 3,485), discrete-time failure analysis was used to model the effect of cumulative metformin exposure on anemia risk.

Results: In ADOPT, compared with sulfonylureas, the odds ratio (OR) (95% CI) for anemia was 1.93 (1.10, 3.38) for metformin and 4.18 (2.50, 7.00) for thiazolidinediones. In UKPDS, compared with diet, the OR (95% CI) was 3.40 (1.98, 5.83) for metformin, 0.96 (0.57, 1.62) for sulfonylureas, and 1.08 (0.62, 1.87) for insulin. In ADOPT, hemoglobin and hematocrit dropped after metformin initiation by 6 months, with no further decrease after 3 years. In UKPDS, hemoglobin fell by 3 years in the metformin group compared with other treatments. At years 6 and 9, hemoglobin was reduced in all treatment groups, with no greater difference seen in the metformin group. In GoDARTS, each 1 g/day of metformin use was associated with a 2% higher annual risk of anemia.

Conclusions: Metformin use is associated with early risk of anemia in individuals with type 2 diabetes, a finding consistent across two RCTs and replicated in one real-world study. The mechanism for this early fall in hemoglobin is uncertain, but given the time course, is unlikely to be due to vitamin B 12 deficiency alone.

Original languageEnglish
Pages (from-to)2493-2499
Number of pages7
JournalDiabetes Care
Issue number10
Early online date14 Aug 2020
Publication statusPublished - Oct 2020

ASJC Scopus subject areas

  • Advanced and Specialised Nursing
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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