- 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.
- 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.
- 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.