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

Significance Statement Because race and sex affect serum creatinine levels independently of GFR, the Food and Drug Administration’s previous creatinine-based metformin contraindication may have inadvertently caused racial and sex disparities in metformin prescription among patients with diabetes and moderate kidney dysfunction. It is unknown whether these disparities were mitigated after a 2016 labeling change to an eGFR-based contraindication. The authors found that before the labeling change, among patients with eGFR of 30–44 ml/min per 1.73 m 2 , Black patients and men were underprescribed metformin for diabetes compared with White patients and women, respectively. Racial and sex disparities were attenuated in patients with eGFR of 30–44 ml/min per 1.73 m 2 after the label change. These results suggest that drug dosing recommendations solely on the basis of serum creatinine may cause racial and sex disparities in its use. 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 m 2 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 m 2 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 m 2 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.