Because the FDA has labeled metformin unsafe for certain patients with renal impairment, many patients with type 2 diabetes may be discouraged from using the drug, according to a research letter published in JAMA Internal Medicine.
“Metformin hydrochloride is the first-line drug for [type 2 diabetes] and is the only oral diabetes drug with evidence for improved cardiovascular outcomes. Despite this, half of the patients with [type 2 diabetes] do not take metformin,” the researchers wrote. “Even in patients who are taking other oral [type 2 diabetes] drugs, only about 70% use metformin.”
In the research letter, they speculated that a reluctance to use metformin in patients with renal insufficiency is likely to blame. Specifically, the label states that the drug is contraindicated when serum creatinine levels are greater than 1.4 mg/dL in women or 1.5 mg/dL in men to avoid lactic acidosis.
However, the researchers noted that the contraindication has been described by some as “overly conservative.”
Further it is at odds with guidelines and recommendations from professional societies, such as the American Diabetes Association, that support metformin use at estimated glomerular filtration rates (eGFRs), which may be a better indicator of renal function than serum creatinine, of 30 mL/min (equating to a serum creatinine of roughly 2 mg/dL) or above.
In their study, the researchers attempted to identify a potential gap in care related to the inconsistency between the FDA label and recommendations from professional societies.
Using data from 2007 to 2012 of patients taking only oral, the researchers evaluated how much metformin nonuse may be attributable to concern safety in patients with renal insufficiency. Sex, age, race/ethnicity, serum creatinine level and eGFR were assessed as predictors of metformin use.
Results showed that rate of metformin use was 90.4% in those with an eGFR greater than 90 mL/min in 2011 to 2012. For patients with eGFRs ranging from 60 mL/min to 90 mL/min, which is below the contraindication cutoff, the rate of metformin use was 80.6%.
For those with eGFRs between 30 mL/min to 60 mL/min, at which metformin is contraindicated according to the FDA but guidelines support cautious use, rates ranged from 48.6% to 57.4%.
For patients with eGFRs lower than 30 mL/min, at which metformin use is discouraged, the rate was 17.9%.
Upon further analysis, the researchers found that approximately 425,000 additional patients would use metformin if the 90.4% use rates seen in patients with an eGFR greater than 90 mL/min were seen among those with eGFRs ranging from 60 mL/min to 90 mL/min. Moreover, an additional 560,000 patients would take metformin if these rates were extended to those with an eGFR of 30 mL/min.
“The FDA is overdue to revisit the contraindication to metformin use in patients with mild to moderate renal insufficiency, which is worsening the care of almost 1 million patients with type 2 diabetes in the U.S.” study researcher Sean Hennessy, PharmD, PhD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, said in a press release.