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Metformin or Sulfonylurea Use in Kidney Disease
Study Questions:
What is the association between treatment with metformin versus sulfonylureas and major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function?
Methods:
The investigators conducted a retrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174,882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 or creatinine ≥1.4 mg/dl for women or ≥1.5 mg/dl for men). Patients were followed up from reduced kidney function threshold until major adverse cardiovascular events (MACE), treatment change, loss to follow-up, death, or study end. The main outcome was MACE, which included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death.
Results:
There were 67,749 metformin and 28,976 sulfonylurea persistent monotherapy users; the weighted cohort included 24,679 metformin and 24,799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48,497 men [98%]; and 40,476 white individuals [82%], with median eGFR of 55.8 ml/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs. 1.2 years for sulfonylurea), there were 1,048 MACE outcomes (23.0 per 1,000 person-years) among metformin users and 1,394 events (29.2 per 1,000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% confidence interval [CI], 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1,000 person-years of metformin use compared with sulfonylurea use.
Conclusions:
The authors concluded that among patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.
Perspective:
This cohort study of US veterans reports that in patients with diabetes who develop reduced kidney function, persistent use of metformin compared with sulfonylurea use was associated with a decreased hazard of MACE. This study adds to the evidence for the beneficial association of metformin compared with sulfonylurea and cardiovascular outcomes among those who develop reduced kidney function. Although there is consensus that metformin is first-line diabetes treatment, metformin is often discontinued when kidney disease develops. In April 2016, the Food and Drug Association (FDA) issued a safety announcement and revised label regarding metformin use with reduced kidney function, which states that metformin can be used safely in patients with mild kidney function impairment and some patients with moderate kidney function impairment, and the current data would support that.
Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Prevention
Keywords: Acute Coronary Syndrome, Creatinine, Diabetes Mellitus, Glomerular Filtration Rate, Glycated Hemoglobin A, Ischemic Attack, Transient, Kidney Diseases, Metabolic Syndrome, Metformin, Myocardial Infarction, Myocardial Ischemia, Primary Prevention, Stroke, Sulfonylurea Compounds, Veterans Health
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