Metformin and Anemia Risk in Type 2 Diabetes

Metformin is the most widely prescribed drug for diabetes and prediabetes globally. It is a first-line safe option for diabetes management.

A recent study published in Diabetes Care has reported that metformin use is associated with early risk of anemia in individuals with type 2 diabetes, a finding which is claimed to be consistent across two RCTs and replicated in one real-world study.

Anemia is a common finding in individuals with type 2 diabetes. Metformin is the first-line therapy for the treatment of type 2 diabetes in most individuals and the most widely prescribed oral antidiabetic medication. Previous results about whether metformin causes anemia and whether or not this is mediated by B12 deficiency in metformin-treated individuals with type 2 diabetes have been inconsistent.

Louise A. Donnelly and associates at the School of Medicine, University of Dundee, Dundee, U.K, undertook a study 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.

Study Design

For the study design, three data sets were analyzed: two from RCTs, A Diabetes Outcome Progression Trial (ADOPT) and the UK Prospective Diabetes Study (UKPDS), and one from routine clinical data of Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS). Anemia was defined as a hemoglobin measure of less than 11 g/dL. Hematological measures were collected at baseline and 3, 6, and 9 years of follow-up.

Findings

• A total of 1,458 individuals (41.8%) had a moderate anemia event during the follow-up period: 745 in current users, 194 in former users, and 519 in never-users.
• 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.

The authors believed that because the mechanisms for metformin-related moderate anemia are unknown, the effects are modest, and the benefits of metformin are proven, avoidance or discontinuation of metformin would not be advocated, even in patients with anemia, but a reduction in Hb in the first few years after initiation of metformin might be anticipated.

"The mechanism for this early fall in hemoglobin is uncertain, but given the time course, is unlikely to be due to vitamin B12 deficiency alone." researchers concluded.

Primary source: Diabetes Care

For the full article, click on the link: https://doi.org/10.2337/dc20-1104