FDA reversal on metformin should save more lives

For decades, the FDA stood by its black box warning that Type II diabetics with kidney impairment should not take metformin, the first-line oral treatment for the diabetes. But last year, after reviewing years’ worth of evidence pointing to the overall safety in kidney patients, the agency finally lifted this restriction.

This reversal is great news, as metformin is the only drug that effectively treats high blood sugar while preventing the eye, kidney, heart, and nerve problems associated with the disease. It also decreases death rates, the ultimate goal of any long-term Type II diabetes treatment, and in fact, any medical treatment at all. Of course, metformin also has its roots in natural medicine as it derived originally from the ancient European folk remedy called French lilac (known in the U.S. as “goat’s rue”).

But I recently came across a headline in the medical news that seemed to stir up unnecessary questions. The headline asked, “Is metformin safe for patients with chronic kidney disease?”

Whenever the mainstream raises questions about metformin, I have found them to be largely misdirected. I suspect they are part of an effort by big pharma to convince physicians to prescribe new, more dangerous, more expensive diabetes drugs that haven’t been proven over the long-term.

Still, I wanted to know more about the new concerns kidney specialists seemed to be raising, so I read the entire article.

Back in the late 20th century, when metformin (then called Glucophage) first entered the U.S. market, there was a firestorm over the idea that it could cause lactic acidosis. Of course, there was no evidence at the time that metformin actually did cause this condition. The concerns stemmed from problems with a related drug, phenformin, and its association with lactic acidosis.

For your background, lactic acid is a metabolic byproduct that your kidneys should filter out. But if you have decreased kidney function, your body can’t effectively excrete it and you may have a propensity to develop lactic acidosis. The same may be true of patients with congestive heart failure and chronic liver disease. (In fact, the same thing also happens in people who engage in excessive exercise. Too much exercise damages joints, the heart muscle, and kidney function, as I reported again last week.)

Metformin stands test of time

Eventually, the FDA approved Glucophage but with a warning that people with kidney impairment shouldn’t take it. The patent has since expired. In fact, you can now get the drug as a safe, inexpensive generic. But the warning to kidney patients remained. Until last year, that is.

Researchers finally came to understand that lactic acidosis results from diabetes itself — and not the drug.

In fact, a large review published in 2006 on 48,000 patients and another in 2008 on 50,000 patients found no increased risk for lactic acidosis in patients taking metformin. These studies showed no elevated risk in patients with normal kidney function or in those with kidney problems. And the benefits of blood sugar control and heart disease prevention remained apparent.

Several other studies also showed decreased mortality in patients with high and moderate kidney function taking metformin. In addition, there was no increase in mortality in patients with low kidney function taking metformin.

Overall, these studies found evidence that men and women who take metformin — regardless of kidney function — experience decreases in mortality without harmful side effects.

So finally, in 2016, after reviewing all of this data the FDA published the new safety announcement, which I mentioned earlier. And now, kidney specialists are talking about it all over again.

Particularly since a recent commentary published in the Journal of the American Medical Association anticipates that doctors will start prescribing metformin to more patients with diabetes who have kidney problems.

Unfortunately, their discussions are often poised as doubt, even though they ultimately agree with the FDA’s new ruling — as was the case with the recent article I mentioned earlier.

Had I not read past the headline, I might have assumed that kidney specialists still erroneously doubted the safety of metformin. When, in fact, the article went into great detail about all of the evidence supporting its use in patients with impaired kidney function.

The technical analyses that go into it all can appear overwhelming. But in the end, there is still no evidence to conclude that metformin is not a safe and effective drug for diabetes, regardless of kidney function.

Once again, this serves as an important reminder to look beyond the headlines before rushing to judgement on ANY therapy.

FDA should apply same caution to newer drugs

All things considered, it is good to see such an abundance of caution when it comes to long-term, first-line drugs like metformin.

It would be helpful to see the same level of scrutiny applied to new drugs that have not stood the test of time.

Of course, doctors who only read the headlines may never learn about the new science. As a senior executive at the American Medical Association (AMA) confided to me almost 20 years ago, according to an in-house (unpublished) AMA member survey, only nine percent of practicing physicians base changes in their medical practice on information they obtain from the published medical literature.

Every member of the AMA gets a copy every week of the Journal.  The rest — if they don’t get past the headlines — must get their information from reading the new drug advertisements

With that in mind, on Thursday, I’ll talk about more problems associated with newer Type II diabetes drugs on the market.

So — stay tuned.



“Is Metformin safe for patients with chronic kidney disease?” Medscape Nephrology (www.medscape.com) 1/30/2017