Metformin is a first-line treatment of choice for type 2 diabetics for controlling blood sugar levels and is the only drug of its kind shown to improve cardiovascular outcomes. There are over 25 million type 2 diabetics in the US, and 10 million of them are taking metformin. But, there are many type 2s that are being discouraged by the FDA from taking metformin due to a claim that it is unsafe for some patients that also suffer from kidney problems. The FDA and professional societies like the American Diabetes Association have different ideas about who metformin is safe for, creating confusion about who should use metformin.
Current metformin guidelines
Currently, the FDA does not approve metformin for certain patients with both type 2 and renal impairment because of fear of lactic acidosis – too much acid in the body which can lead to kidney injury, sepsis, liver failure, and heart failure. The FDA determines whose kidneys are healthy enough for metformin based on creatinine levels. The FDA recommends against metformin for women whose creatinine levels are above 1.4 mg/dL and for men’s who are above 1.5 mg/dL.
Professional guidelines disagree with those FDA standards, thinking that their numbers are too conservative. Professional societies instead suggest that use of metformin should be based on estimated glomerular filtration rates (eGFRs), which describe the flow rate of filtered fluid through the kidney. If a patient’s eGFR is above 30 mL/min (which is roughly equal to a serum creatinine level of 2 mg/dL), professional guidelines believe that metformin is safe to use.
Challenging the FDA’s recommendations
Researchers Sean Hennessy, PharmD, PhD of Penn Medicine and James H. Flory MD, MSCE of Weill Cornell Medical College published a letter that challenges the FDA’s guidelines saying that they are too strict and professional guidelines should be followed instead. They conducted a study that analyzed if there is a gap in care due to the inconsistencies between professional recommendations and FDA labeling. They examined data from 2007 to 2012 of patients taking only oral medication from the National Health and Nutrition Survey so they could evaluate the number of people that are being blocked from using metformin by the FDA due to a concern for safety.
Around 48 to 57 percent of patients with an eGFR between 30 and 60 mL/min, supported by professional guidelines and in opposition to the FDA guidelines, are taking metformin. In patients with eGFRs greater than 60 to 90 mL/min the rate of patients taking metformin is 80.6 percent. As stated by Hennessy, one of the authors of the study, “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 US.” Current research and studies support the expansion of metformin use with the appropriate dosage reductions and careful follow-up for patients with moderate chronic kidney disease. FDA citizen petitions were filed in 2012 and 2013 requesting that the metformin guidelines be relaxed and reframed to reflect GFR measurements, but so far no amendments have been made.