Invokana warning: foot and leg amputations

Invokana is an SGLT-2 inhibitor. The FDA has just asked Johnson & Johnson to display a big box warning about foot and leg amputations:

The FDA noted that results of one clinical trial showed that over the course of a year the risk of amputation in patients treated with Invokana was equivalent to 5.9 out of 1,000, compared with 2.8 out of 1,000 for patients given a placebo.

I’m not going to get excited about this until they find some causation. It’s not like it couldn’t just be random, as the base risk for amputation is relatively pretty high in their test population anyway. Remember how insulin causes heart disease?

I think a better warning would be “control your diabetes because there is an increased risk of amputation if it remains uncontrolled”

It should be noted that the warning is on the basis of two trials, not just one. However as Doc points out, and I am trying to find the studies to see what their populations were, it is probably very high risk T2’s. Which probably doesn’t mean much to the consumers of our web-niche.

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You know, the more I think about this the angrier I get with the FDA.

Requiring that a big box warning on the drug could be enough to scare someone into not taking a drug that could be of immense help to them.

Just another way that the FDA impedes progress of drugs that are needed by the American people.

Yes, it would be nice to go back to the days of letting the Dr’s treat patients. Instead, since pharma spends so much money on advertising directly to patients, we need to put the “don’t smoke” warning on everything…

I am not with you on this, Doc :slight_smile: Two studies, both with exactly the same double rate on amputation, and double blind placebo control groups – that would make me worried too. This is rational to me.

Could be something to be worried about, or it could be the drug has a favorable profile for certain patient groups and not others. The problem with the label proposed, is that it doesn’t weigh the positive benefits with the negative.

For instance, In late stage cardiac disease every cardiac drug destroys the kidneys, and the kidney drugs destroy the cardiac system, and which you choose is based on which will keep the patient alive and healthier the longest. No good choices, just less bad.

A more nuanced label, would say if you meet these criteria, you should know you have a higher risk of amputation. More information is needed. Which is why educating physicians rather than consumers should be the default.

@Michel Causal relationship? Also, as @Chris mentioned, what are the details on those trial groups? If the groups are moderately long term T2-diabetics with A1c over 8 or 9, then a 50% variance between the drug treated and untreated groups becomes less significant.

But that’s not box FDA black box labels work…

Exactly… nowhere near enough information in that paragraph to determine if it’s meaningful. Fortunately we have experts whose job it is to sort out what’s bs and what’s not and what treatment benefits outweigh risks… they’re called doctors.

I do not agree with the fda requiring certain drug manufacturers to print alarming warnings right on the front of the package but not others… it opens the door to competitors lobbying the FDA for competitors medications to have more alarming warnings… (this is exactly what happened with afrezza) it also effectively is a mechanism of a government bureaucracy picking winners and losers— which they’re notoriously horrible at.

It is the doctors job to be informed about the risks of the medications they provide and make informed decisions. Putting a big alarming warning on a box accomplishes nothing but harms people who might have potentially benefitted from the drug, but now won’t because the box is too scary

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Clearly not causal, just correlated.

But, if I am a naive user, I want to know. I don’t agree with you or @Sam. I don’t want to have to dig through research to find out something that may be a sign. Let me make the decision of whether or not to go ahead, but tell me if there is a potential concern.

I think it’s a reasonable decision. It is not a single study. There is cause for concern. But I agree the boundaries are not clear-cut.

We don’t even know from that summary whether or not he control/ placebo group had diabetes… if they did, what treatment they were using, etc etc… hardly any info there. And if the control group did not have diabetes is it highly surprising that the test group had a higher incidence of diabetes complications? This is why I’m really not into trying to research things on the Internet-- there’s just too little information actually there and what we do find it we often do not understand the context of

I don’t want to dig through research either… that’s my doctors job…

I sent in a news release – you should feel free to look up the actual studies. But I have the feeling that the FDA did read them… And, if these studies are half-way decent, two studies giving the same result (doubling of amputations) should be a sign of concern.

I have trusted my doctors and my sons’ for too long:-) Now I don’t trust anyone with my health or his except as advisors – and I make sure to sanity check on them.

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Dug through some articles and I found the study group was just as I suspected. Average age is 64 y.o. Average A1c of 8.3%, 14 year average duration of T2, pre existing renal disease and high risk for cardiovascular disease. A not insignificant percentage of the group had a history of amputation. This was the renal branch of the study, just one of those referenced by the FDA.

In deference to @Michel, there is likely a moderately large cohort of people like this who would be prescribed this drug. I’m sure the warning box will save or delay a few amputations, but how do we measure the number of patients (and doctors) who are scared away from using a drug that could help them?

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