Metformin safe for most diabetics with kidney disease

Metform, a longtime and low-cost drug used to treat diabetes, is safe for most patients who also have chronic kidney disease, according to new research.

Researchers found metformin, a long-time and low-cost drug used to treat diabetes, is safe for most patients who also have chronic kidney disease. File Photo by Brian Kersey/UPI | License Photo
Researchers found metformin, a long-time and low-cost drug used to treat diabetes, is safe for most patients who also have chronic kidney disease. File Photo by Brian Kersey/UPI | License Photo

Johns Hopkins Medicine investigators examined data from more than 150,000 patients in two studies, finding the oral drug’s association with lactic acidosis development occurred only among those with severely decreased kidney function. Their findings were published Monday in the Journal of American Medical Association Medicine.

Metformin hydrochloride, which is marketed as Glucophage, and under other trade names, was discovered in 1918.

Although it is recommended as the first-line medication for type 2 diabetics, approximately 1 million patients in the United States with mild to moderate kidney disease don’t receive metformin, Hopkins researchers note. Physicians avoid prescribing the drug for patients who have chronic kidney disease because of concerns for drug accumulation and lactic acidosis.

That originally led to the withdrawal of the drug from the U.S. market in 1978, but it was found to be less potent than other glucose-lowering biguanides, and was subsequently reintroduced in France in 1957 and the United States in 1995.

The Food and Drug Administration recently revised its labeling of metformin so it could be used by some chronic kidney disease patients.

About 19 percent of those in the United States with diabetes also have kidney disease, but studies of the drug’s safety for those with both diseases had inconclusive results.

“Our study demonstrates that the first-line and common diabetes medication is safer in patients with CKD than once thought,” Dr. Morgan Grams, an associate professor of medicine and epidemiology at the Johns Hopkins University School of Medicine, said in a press release. “From a public health perspective, the potential benefits of using metformin for patients with diabetes and CKD are vast, given the increasing number of people affected with both diseases worldwide.”

Researchers analyzed medical records for 75,413 patients with a mean age of 60 who have diabetes and were members of Geisinger Health System in Pennsylvania from 2004 to 2017. They used computer-based statistical models to analyze the risk of developing acidosis among metformin users, comparing it with nonusers. The models were adjusted for conditions that included cardiovascular disease and smoking status.

Of the patients, 45 percent were taking metformin at enrollment in the study and the remaining patients were subsequently prescribed metformin during a 5.7-year follow-up period.

The researchers found an association between metformin use and acidosis only in patients with severely decreased kidney function, which is defined as an eGFR of less than 30 mL/min/1.73 m2. It was more more than double the risk in patients with severely decreased kidney function who took another diabetes drug. A normal eGFR is 90.

“Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m2,” Grams said.

Researchers also compared new metformin users with initial users of another class of diabetes medications — sulfonylureas — and different categories of CKD stages. They analyzed records for 82,017 patient records covering 2010-2014 from MarketScan, which is a database of inpatient and outpatient claims data from 350 private health systems.

New metformin users’ results compared favorably with new sulfonylurea users, and with the MarketScan patients, the researchers reported.

By Allen Cone