Will Bydureon become the next metformin?
While it may seem like the FDA is doing everything within their power to take away tools used to fight diabetes, this is not the first, and sadly probably won’t be the last time the agency was overly conservative in approving a potentially ground breaking therapy option. Although widely prescribed today there was time when many believed metformin would never make it to the market. Since history has a way of repeating itself, it may be useful to take a look back at how metformin almost never made it.
Way back in 1957, three researchers working for the US Vitamin Company discovered a drug called Phenformin. The following year clinical trials began and the drug was approved by the FDA in 1995. Marketed as DBI by Ciba-Geigy the drug was considered a major hit until the late 70’s when it was discovered patients using the drug experienced a high incidence rate of lactic acidosis, a condition which was fatal in 50% of the cases. The FDA intervened and the drug was officially withdrawn from the market in November 1978.
Metformin, also from the biguanide class of drugs, was actually discovered way back in the 1920’s. The drug was largely ignored until the mid 1940’s when researchers discovered the drug could reduce glucose levels and in 1957 French physician Jean Sterne published the first clinical trial of metformin as a treatment for diabetes. The United Kingdom first approved the drug in 1958, followed by Canada in 1972. Yet the FDA did not approve the drug until 1995. Today metformin is the most widely prescribed anti-diabetic agent with more than 42 million prescriptions filled in 2009. It is not in overstatement to say that metformin is the standard of care and first choice among physicians when treating their patients with type 2 diabetes.
Yet Metformin almost never made it to market, thanks in large part to the issues that lead to Phenformin being withdrawn from the market in 1978. Like metformin, phenformin is also from the biguanide class of drugs, and given the issues with the drug it does make perfect sense that the FDA would take a long and hard at metformin before approving the drug. However, should it have not taken 37 years for metformin to be approved? Did they agency not see the same data that allowed the U.K. to approve the drug in 1958, or Canada in 1972?
As noted earlier history has a strange way of repeating itself and the metformin/phenformin is a perfect example of the FDA being overly cautious. Yes it is perfectly understandable that the agency would seek detailed data on metformin and yes it also understandable they would be skeptical given the experience with phenformin. It’s even reasonable that they would take longer to approve the drug here in the US, given the differences between the US, the U.K. and Canada. As it has been said many times the Americans and the British are two common people separated by a common language. And it understandable that our good neighbors to the north would move quicker than we do after all they invited the great game of ice hockey.
What is not understandable is the gap of time between when the drug became available in the U.K and when it became available here in the US. Frankly that isn’t a gap, that’s a hole the size of the Grand Canyon. The scarier thought is just how perilously close the agency came to not approving the drug. Just as things stand today, back in 1995 diabetes was major and growing problem. Just as today, back in 1995 patients needed more not less options for treating their diabetes. Just as today, the agency was not focused on science but operating from a perspective of fear, the fear of making a mistake.
There are also other parallels between metformin and Bydureon. Just as Bydureon is not the perfect drug or silver bullet for treating type 2 diabetes neither is metformin. Metformin has well known gastrointestinal side effects and there are patients who cannot tolerate metformin therapy. Still looking at the overall risk/reward profile of metformin the benefits of the drug clearly outweigh the risk factors. Additionally if a patient cannot tolerate metformin there are other therapy options available. This is also the case with Bydureon.
Pause for a moment and think of how things may have been different had metformin been available in the 1960’s or 70’s. Would we be facing a diabetes epidemic as we are today? Would therapy non-compliance be the issue it is today? Would we still be facing a situation where nearly two-thirds of all patients are not adequately controlling their diabetes? Frankly there is no way we can answer these questions. The simple fact is we will never fully understand the impact of the FDA lengthy approval process for metformin, we can only see the results of their overly cautious approach.
Let’s hope for the sake of the millions of patients with type 2 diabetes that the FDA does not take another 37 years to approve Bydureon. Let’s hope the agency learns from their past mistakes and approves this desperately needed medication. We’re all for being diligent and thorough but it is equally dangerous to experience paralysis by analysis. Finally let’s hope that the agency understand that there is no such thing as truly adverse event free medication and that there will risks with any drug. That they take the benefits and risks into consideration side by side and conclude that the Bydureon risk/reward profile is acceptable, especially in light of the fact that patients with diabetes need newer and better medications.
The one thing we don’t want to see is history repeating itself yet again. This would be a true injustice and as Abraham Joshua Heschel wrote; “An act of injustice is condemned, not because the law was broken, but because a person has been hurt.”