Cardiovascular Safety and Metformin Use

For patients with diabetes and kidney disease, metformin could lower cardiovascular risk.

A new study published in JAMA helps fill in gaps related to metformin use by including a population generally excluded from other diabetes medication trials – people with reduced kidney function.

Metformin can accumulate in the kidneys, which initially led the FDA to issue a safety warning restricting its use for patients with abnormal serum creatinine levels. While the FDA has since softened its stance, data remain limited for how to use the frontline diabetes drug in patients with reduced glomerular filtration rates (eGFRs).

“Until recently the use of metformin in patients with diabetes and impaired kidney function was cautioned against due to safety concerns. While we have data on the effectiveness of metformin for those with normal kidney function, we wanted to see if metformin had cardiovascular benefits for those with kidney disease,” said Christianne L. Roumie, M.D., corresponding author on the study and associate professor at Vanderbilt University Medical Center.

An Impressive Scale

 Roumie collaborated with colleagues from the Veteran Administration Tennessee Valley VA Health System and the Vanderbilt Departments of Biostatistics and Health Policy to review 174,882 veteran patient records for the study.

They identified patients who received persistent single-agent therapy for diabetes after developing reduced kidney function (either an eGFR of less than 60 mL/min/1.73 m2 or serum creatinine level of 1.5 mg/dL for men or 1.4 mg/dL for women).

The researchers focused on two classes of glucose-lowering medications: metformin and sulfonylureas (glyburide, glipizide, or glimepiride). They compared cardiovascular events among two groups of patients: those who used metformin and those who used sulfonylureas between 2001 and 2016. In total, they compared 24,679 patients who received metformin to 24,799 patients who received sulfonylurea. Most patients stayed on their medications for about one year after they developed reduced kidney function.

Cardiovascular Outcomes

The study was designed to measure major adverse cardiovascular events (MACE) associated with using either drug.

The researchers evaluated cardiovascular events including hospitalizations for acute myocardial infarction, ischemic or hemorrhagic stroke, transient ischemic attack, and cardiovascular-related deaths.

Metformin users experienced 1,048 adverse events while sulfonylurea users experienced 1,394, or 23.0 and 29.2 per 1,000 person-years of medication use, respectively. After adjustment for other risk variables, this amounted to a 20 percent reduced risk with metformin compared to a sulfonylurea.

The authors noted, “Continued treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE among patients with diabetes and reduced kidney function.”

Informing Clinical Practice

“We believe these results should encourage providers to continue use of metformin in patients with mild-to-moderate kidney disease.”

While metformin is known to control blood glucose, many practitioners often stop it for patients with reduced kidney function. Roumie is hopeful this new study could change minds.

“The effectiveness of metformin demonstrated in this study will further support a potential change in prescribing practices for these patients. We believe these results should encourage providers to continue use of metformin in patients with mild-to-moderate kidney disease.”