The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD

Abstract

Background: In 2016, the Food and Drug Administration (FDA) changed labeling regarding metformin contraindications in patients with diabetes and CKD from using serum creatinine-based thresholds to using eGFR-based thresholds. Because race and sex affect serum creatinine levels independently of GFR, the earlier creatinine-based contraindication may have inadvertently caused racial and sex disparities in metformin prescription among patients with low eGFR.

Methods: In an analysis of 15,946 Black and White primary care patients with diabetes and eGFR≥30 ml/min per 1.73 m² in a large health system (the primary cohort), we assessed the association of race and sex with metformin prescription across eGFR level before and after the FDA label change. For a replication cohort, we meta-analyzed data from 36 cohorts with 1,051,723 patients from OptumLabs Data Warehouse.

Results: In the primary cohort, before the label change, Black patients with eGFR of 30-44 ml/min per 1.73 m² were prescribed metformin less often than White counterparts (adjusted prevalence ratio [aPR], 0.65; 95% confidence interval [95% CI], 0.52 to 0.82); this disparity was significantly attenuated after the label change (aPR, 0.90; 95% CI, 0.74 to 1.09; P value for interaction by period =0.04). Results were consistent in the replication cohorts. Men with eGFR of 30-44 ml/min per 1.73 m² received metformin prescriptions less often than women counterparts before the label change; this was nonsignificantly attenuated after the label change, but we found significant attenuation in the replication cohorts (aPR_{pre-label change}, 0.76; 95% CI, 0.73 to 0.79; aPR_{post-label change}, 0.85; 95% CI, 0.83 to 0.88; P value for interaction by period <0.001).

Conclusions: The metformin label change to an eGFR-based contraindication may have reduced racial and sex disparities in metformin prescription in moderate kidney dysfunction.

Keywords: FDA drug label; chronic kidney disease; clinical epidemiology; creatinine; disparities; estimated glomerular filtration rate; glomerular filtration rate; metformin.