April 24, 2018

Marcum study finds metformin has mortality benefits even with low kidney function

Collaborative research between UW School of Pharmacy and VA Puget Sound looked at 175,000 patients

Assistant Director of the Plein Center and Bailey Faculty Fellow Zach Marcum

In a recent study, researchers at the University of Washington and the VA Puget Sound Health Care System have found that an important diabetes drug can be used safely among a high-risk patient population – those with poor kidney function. They concluded metformin should be prescribed preferentially over sulfonylureas in this group of patients based on overall mortality benefits.

In 1995, the FDA approved metformin for patients with Type 2 diabetes; however, the label advised clinicians to avoid prescribing metformin to patients with impaired kidney function because of concerns about lactic acidosis. But in 2016, the FDA endorsed metformin’s safety in patients with mild-to-moderate kidney function impairment.

To determine whether risk for death differs following initiation of metformin monotherapy or sulfonylurea monotherapy among veterans with Type 2 diabetes and chronic kidney disease, Zach Marcum, Assistant Director of the Plein Center for Geriatric Pharmacy and Bailey Faculty Fellow, and colleagues conducted this cohort study of 175,000 older adult patients with diabetes and chronic kidney disease who initiated these drugs at Veterans Affairs medical centers between 2004 and 2009.

Their results showed that metformin had significant benefits over sulfonylureas across the stages of kidney function. Metformin use was associated with a 36% lower risk for death overall.

 “This study should be reassuring to clinicians and to diabetic patients with impaired kidney function. Metformin should be prescribed preferentially over sulfonylureas in this group of patients.” – Paul Mueller, MD, MPH, FACP, reviewing the study for the New England Journal of Medicine Journal Watch

Metformin had been restricted as it was thought to have an unfavorable risk/benefit profile among people with low kidney function. However, in their research, Zach and the team found that metformin had mortality benefits.

Although residual confounding is possible, this study shows that initiation of metformin monotherapy versus sulfonylurea monotherapy among patients with Type 2 diabetes and mild-to-moderate kidney function impairment is associated with lower risk for death, which should be reassuring to clinicians and to diabetic patients with impaired kidney function.

The data reviewed were from 2003 to 2009, which is important because today people wouldn’t be prescribed a sulfonylurea as first-line treatment for type 2 diabetes, but during this timeframe there were substantial numbers of people being prescribed either metformin or a sulfonylurea as initial monotherapy.

The team grouped people into different levels of kidney function based on severity of impairment. They found benefits for people using metformin in both absolute and relative terms. Many studies stop at relative risk, but this one found a benefit to absolute risk as well. The largest absolute risk reduction was observed among individuals with the moderately-severely reduced kidney function. This is a group of patients for whom the FDA label currently advises to not start metformin. Future research is needed to confirm these findings.

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