Metformin use tied to early risk of anaemia in type 2 diabetes

  • Donnelly LA & al.
  • Diabetes Care
  • 14 Aug 2020

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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  • Metformin use was associated with an early reduction in haemoglobin (Hb) and increased rates of moderate anaemia in patients with type 2 diabetes (T2D), and this finding was consistent across two randomised controlled trials (RCTs) and replicated in one real-world study of routinely collected data.

Why this matters

  • Because the mechanisms for metformin-related moderate anaemia are unknown, the effects are modest, and the benefits of metformin are proven, the authors do not advocate avoidance or discontinuation even in patients with anaemia, but a reduction in Hb in the first few years after initiation might be anticipated.

Study design

  • Association between metformin use and anaemia risk in T2D and the time course for this were evaluated in the A Diabetes Outcome Progression Trial (ADOPT; n=3967) and UK Prospective Diabetes Study (UKPDS; n=1473) RCTs.
  • The cumulative effect was evaluated in the observational Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) population (n=3485).
  • Funding: Medical Research Council.

Key results

  • In ADOPT, compared with sulphonylureas, the OR for anaemia was 1.93 (95% CI, 1.10-3.38) for metformin and 4.18 (95% CI, 2.50-7.00) for thiazolidinediones (TZDs).
  • In UKPDS, compared with diet, the OR for anaemia was 3.40 (95% CI, 1.98-5.83) for metformin, 0.96 (95% CI, 0.57-1.62) for sulphonylureas and 1.08 (95% CI, 0.62-1.87) for insulin.
  • In ADOPT, Hb and haematocrit levels dropped by 6 months in both metformin and TZDs groups with no further Hb decrease between 3 and 5 years.
  • In UKPDS, Hb levels dropped by 3 years with metformin treatment vs other treatments.
  • At 6 and 9 years, Hb levels were reduced in all treatment groups with no greater further fall seen in the metformin vs diet-treated group (0.49 g/dL [95% CI, -1.64 to 2.62] vs 0.50 g/dL [95% CI, -1.71 to 2.72] fall from 3 to 9 years).
  • In GoDARTS, each 1 g/day of metformin use was associated with a 2% increased annual risk of anaemia.


  • Lack of vitamin B12 measurement.
  • Post hoc analysis of RCT data.