Metformin and the Risk of Anemia of Advanced Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus

This retrospective cohort study determines whether metformin monotherapy or combination therapies can decrease anemia risk in the progress of advanced chronic kidney disease for patients with type 2 diabetes mellitus. The data set was obtained from the National Health Insurance Research Database, containing 1 million randomly selected beneficiaries. After matching, 9303 pairs (1:1) of metformin users and nonusers were acquired. Every patient was individually recorded from 1997 to 2012 to identify anemia incidence (hemoglobin <9 gm/dL). Cox regression models were used to compute hazard ratios and 95% confidence intervals (CIs). There were 305 (0.7%) and 76 (0.8%) erythropoietin-stimulating agent cases in the metformin and non-metformin cohorts over a mean follow-up period of 6.8 and 5.6 years. After matching, the use of metformin decreased the risk of usage of erythropoietin-stimulating agents with an adjusted hazard ratio of 0.76 (95%CI, 0.45-1.29) for dosage of <357 g to 0.30 (95%CI, 0.17-0.56) for >1368 g. The combination of metformin and dipeptidyl peptidase-4 inhibitors decreased with a hazard ratio of 0.42 (95%CI, 0.18-0.99), compared to metformin alone. Metformin combined with dipeptidyl peptidase-4 inhibitors is superior to metformin monotherapy or non-metformin antidiabetic therapies for reducing the risk of anemia in the progress of advanced chronic kidney disease among patients with type 2 diabetes.