Continued monotherapy with metformin, compared with a sulfonylurea, is associated with a lower risk for major adverse cardiovascular events (MACE) among patients with type 2 diabetes who experienced reduced kidney function.

Christianne L. Roumie, MD, MPH, of the Nashville VA Medical Center, in Nashville, Tennessee, and colleagues published the new findings in JAMA, which corroborate previous observational data.

In a propensity-score matched cohort study of 49,478 mostly male veterans (median age 70 years; 82% white) who reached an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 or crossed a serum creatinine threshold of 1.5 mg/dL for men or 1.4 mg/dL for women, significantly fewer MACEs occurred in those receiving metformin vs sulfonylurea monotherapy: 23.0 vs 29.2 per 1000 person-years. Metformin users were 20% less likely to experience a MACE, including hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death, than users of the sulfonylureas glipizide, glyburide, or glimepiride.

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In 2016, the FDA stated that metformin can be safely used in patients with an eGFR of 45 to 60 mL/min/1.73 m2, but the FDA recommended against its use in patients with an eGFR 30 to 45 mL/min/1.73 m2.

“Patients with reduced eGFR may use metformin with frequent monitoring and dose reduction, but metformin is contraindicated at an eGFR less than 30 mL/min/1.73 m2,” Dr Roumie’s team noted. Study results cannot be generalized to patients who already have a reduced eGFR at the time of metformin initiation.

“The study further supports the use of metformin as the first-line treatment to which other diabetes medications are added, even as early chronic kidney disease develops,” Deborah J.Wexler, MD, MSc, of Massachusetts General Hospital in Boston, commented in an accompanying editorial. It is possible that some study patients had acute kidney injury rather than progression to chronic kidney disease (CKD).

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Roumie CL, Chipman J, Young Min J, et al. Association of treatment with metformin vs sulfonylurea with major adverse cardiovascular events among patients with diabetes and reduced kidney function [published online September 19, 2019]. JAMA. doi:10.1001/jama.2019.13206

Wexler DJ. Sulfonylureas and cardiovascular safety: The final verdict? [published online September 19, 2019]. JAMA. doi:10.1001/jama.2019.14533