In 2016, the US FDA changed labeling regarding metformin contraindications in patients with diabetes and chronic kidney disease (CKD) from using thresholds based on serum creatinine to using thresholds based on estimated glomerular filtration rate (eGFR). Serum creatinine levels are affected by race and sex independently of GFR; the earlier contraindication based on serum creatinine may have caused racial and sex disparities in metformin prescription among patients with low eGFR.
Jung-Im Shin, MD, and colleagues performed an analysis to assess the association of race and sex with metformin prescription across eGFR level prior to and following the FDA label change. The analysis included data on 15,946 Black and White primary care patients with diabetes and eGFR ≥30 mL/min/1.73 m2 in a large health system (the primary cohort). Data for a replication cohort was meta-analyzed from 36 cohorts with 1,051,723 patients from OptumLabs Data Warehouse.
Before the label change, Black patients in the primary cohort with eGFR 30 mL/min/1.73 m2 to 44 mL/min/1.73 m2 were prescribed metformin less often than White counterparts (adjusted prevalence ratio [aPR], 0.65; 95% confidence interval [CI], 0.52-0.82). Following the label change, the disparity was significantly attenuated (aPR, 0.90; 95% CI, 0.74-1.09), P for interaction by period=.04. In the replication cohorts, results were similar.
In analysis of disparities by sex, prior to the label change, men with eGFR 30 mL/min/1.73 m2 to 44 mL/min/1.73 m2 received prescription for metformin less often than women; the disparity was nonsignificantly attenuated after the label change. There was significant attenuation in the replication cohorts (aPRpre-label change, 0.76; 95% CI, 0.73-079; aPRpost-label change, 0.85; 95% CI, 0.83-0.88; P for interaction by period <.001).
In conclusion, the authors said, “The metformin label change to an eGFR-based contraindication may have reduced racial and sex disparities in metformin prescription in moderate kidney dysfunction.”