Taking metformin was not associated with incident lactic acidosis requiring hospitalization in patients with estimated glomerular filtration rates (eGFRs) between 30 and 59 mL/min/1.73 m2, according to a study of two community cohorts of patients with diabetes. However, metformin use was associated with an increased risk of acidosis in patients with an eGFR less than 30 mL/min/1.73 m2 (adjusted hazard ratio, 2.07; 95% CI, 1.33 to 3.22). The results, which included more than 150,000 patients, led the study's authors to support cautious use of metformin in patients with type 2 diabetes and an eGFR of at least 30 mL/min/1.73 m2.
The study was published in the July JAMA Internal Medicine. The following commentary by Alexander A. Leung, MD, MPH, FACP, and Raj S. Padwal, MD, MSc, was published in the ACP Journal Club section of the Oct. 16 Annals of Internal Medicine.
Metformin is recommended as first-line therapy for type 2 diabetes because of its low cost, proven safety record, and potential cardiovascular benefits. However, whether metformin can be safely used in patients with chronic kidney disease (CKD) is a matter of debate.
Lazarus and colleagues examined the risk for hospitalization for acidosis associated with metformin compared with another antidiabetes agent in 2 risk-adjusted cohorts. Consistent with previous reports, risk for acidosis was higher only in patients with eGFR < 30 mL/min/1.73 m2. The major limitation was reliance on a nonspecific diagnostic code to identify cases of lactic acidosis, which raises the potential for misclassification and outcome heterogeneity and may bias the results to the null.
Overall, the evidence supports the safety of metformin in patients with stage 3 or lower CKD. Accordingly, recent guidelines and regulatory policy recommendations have extended its use to individuals with mild to moderate kidney impairment (eGFR 30 to 59 mL/min/1.73 m2).