The study, conducted at the University of North Carolina at Chapel Hill, showed 22 of 100 randomly selected patients on metformin had one or both of the contraindications.
“Our findings are consistent with several recent studies in Europe that documented similar rates of inappropriate metformin prescribing,” said Dr. Cheryl Horlen, who conducted the research as a pharmacy resident at UNC. “We are concerned that these patients may be at risk of a serious medical condition known as lactic acidosis, which can be life-threatening.”
In the first 14 months after its release in the United States, the Food and Drug Administration received reports of 47 confirmed cases of lactic acidosis associated with metformin, said Horlen, now an assistant professor of pharmacy practice at Campbell University. Those cases had a 42 percent mortality rate. In the absence of contraindications, the drug is considered safe and effective.
A report on the study appears as a letter in the May 15 issue of the Journal of the American Medical Association. Besides Horlen, authors are Drs. Robb Malone, Betsy Bryant, Timothy Carey, Michael Pignone and Russell Rothman of the UNC department of medicine faculty and Dr. Betty Dennis of the UNC Hospitals Pharmacy.
“We performed a retrospective review of hospital charts of patients receiving metformin through the outpatient pharmacy at an academic medical center,” Horlen said. “We found 241 patients who had two or more prescriptions for metformin within a nine-month period and then randomly selected 100 of those for the chart review.”
She and colleagues found 14 of the patients had congestive heart failure only, five had kidney dysfunction only and three had both. The mean age of patients was 60; half were women and half were black.
“Only two patients had documentation in their medical records that providers had considered the metformin contraindications,” Horlen said. “Because our assessment of the prevalence of contraindications to metformin use relied on a chart review, it might have underestimated the frequency of contraindications. It also was difficult to determine whether providers were aware they were prescribing metformin against what is called a black box warning, which is a specific warning with a black border around it to attract attention.”
Doctors and other health care providers should consider improving documentation of the risk of lactic acidosis and offer counseling for patients who receive the drug, she said. Considering the new study and the European results, there is no reason to believe metformin prescribing practices differ much in other parts of the United States.
"Although this was a relatively small study, the fact that almost one in four prescriptions for metformin were being prescribed against the black box warning may be significant,” said Rothman, a Robert Wood Johnson Clinical Scholar at UNC. “With more than 25 million prescriptions of metformin written a year, the potential for adverse events needs to be taken very seriously. More research will need to be performed to ensure that patients are receiving optimal care."
Note: Horlen’s number is (910) 678-0121, Rothman’s (919) 966-1274, Pignone’s (919) 966-2276.
By DAVID WILLIAMSON
UNC News Services
Journal
JAMA