April 9, 2008

Exubera Linked to Lung Cancer -- Is Januvia Next?

UPDATE (April 2, 2013): Before you take Byetta, Victoza, Onglyza, or Januvia please read about the new research that shows that they, and probably all incretin drugs, cause severely abnormal cell growth in the pancreas and precancerous tumors. You'll find that information HERE.

Original Post:

Today's business news included a story about how Pfizer has found a significantly higher incidence (not risk, actual incidence) of lung cancer in people taking its inhaled insulin Exubera.

Pfizer is no longer marketing Exubera in the U.S., but it continues to sell it to patients who had been on it and test it in clinical trials.

Inhaled Insulin is Cancer for Mannkind - Forbes

What is most disturbing about this story is not just that this cancer finding emerged after years during which Pfizer assured the medical community that Exubera was completely safe for the lungs. That's nasty enough. But what is most disturbing, to me, is how this finding highlights how inadequate the current system of clinical trials is for determining if a drug that uses a novel mode of action promotes cancer.

Yes, the clinical trials will determine if exposure to the drug causes cancer to grow in a test tube and it will also test to see if 60 times the human dose of the drug causes cancers in rodents. But whether a normal dose of the drug changes the balance of the human body in a way that might allow cancer to grow where it otherwise would not grow is NOT investigated. Nor do most clinical trials run long enough for slow growing human cancers to become evident. It is only after a drug is used by tens of thousands of paying customers that its ability to cause cancers usually emerges, as was the case here with Exubera.

Few patients ever used Exubera. But I have been writing for more than a year now about why the most frequently prescribed new diabetes drug, Januvia, poses a very real cancer risk that has not been investigated at all. The way Januvia promotes cancer makes it very tough to connect those cancers to the drug, since the cancers it may promote is melanoma.

When someone is squirting a drug into their lungs and develops a lung cancer, the doctor may make the connection between the drug and the cancer. When someone is taking a pill to lower their blood sugar and dies of melanoma, the doctor probably won't. They'll think, "Too much sun." Not, "Januvia turned off the enzyme the body relies on to kill melanocytes that have gone malignant."

Doctors do not understand that Januvia inhibits the action of a protease, DDP-4, that appears to play a part in the immune system's fight against cancer. Doctors know only that that inhibiting DPP-4 raises GLP-1. I suspect if you ask your doctor what DPP-4 is, you will not get a coherent answer, because busy doctors have very little understanding of the biochemistry of most of the drugs they prescribe. And even if your doctor does know what DPP-4 is, he isn't likely to know that DPP-4 is used in the immune system and that it is active in the brain. Mine didn't.

And when a pretty drug company rep chirps, "DPP-4 inhibitors lower glucose" you doctor certainly didn't ask, "When you inhibit this molecule with your drug, what else are you inhibiting?" Even worse, when approving the drug, the FDA didn't ask that question either. There was NO study submitted as part of the drug approval process for Januvia that investigated the impact of inhibiting DPP-4 on its specialized functions throughout the immune system.

We do know that another drug, Ankinra, which also ends up inhibiting DPP-4, did raise the incidence of melanoma in the population who took the drug for a longer time than the Januvia trials lasted. But because the clinical trials for Januvia did not last longer than two years and the cancers involved take more than two years to develop, if we do get a rash of unnecessary cancer deaths due to this drug, the connection may never be made.

This is very worrisome. Ever since I first published the links to the research conneting DPP-4 inhibition with melanoma I have been waiting for someone to write me, "Foolish woman, there is no reason to worry about this issue because . . . " followed by a long list of cogent reasons involving knowledge of biochemistry and physiology far superior to mine.

But no one has. One researcher told me that I had raised a valid issue but that no research had been done to look into it. And that's all I heard.

In an ironic way, the Exubera report is GOOD news, because the connection was made between the cancer and the drug. With Januvia, that may not happen. So I urge you to report to the FDA Medwatch Program any skin cancer you contract while taking Januvia. If you hear of any such cancer occurring in a person taking Januvia, insist that they get their doctor to report it to the FDA. This may be the only way we save hundreds or even thousands of lives from a very nasty and very unnecessary death.


Laura Williams said...

There's a new plan up here to -speed up- the drug approval process. It's getting support from AIDS patients, which I completly understand: they're often in an 'approve this drug before I die' situation.

But it really makes me nervous to think of fast tracking drugs that arn't in that category.

The Old Man and His Dog said...

Why is it that they test lab rats on doses several hundred times greater than the normal human dosing anyway? I always wondered this question quietly to myself. Why not just do it at the rat equivalent to the human dose? Why is more always better when instead they should be looking for the other effects of a normal dosage long term?

Anonymous said...

Once again your right on. All the drug companies care about is the bottom line (how much money can we make before they realize this drug is lethal).
As you say doctors will never connect the pill with the disease. This is the same story with statins and the increase of liver disease.
Recently there was the tie in to Singulair and it's effect on mood swings and suicidal tendencies. When this drug is advertised on tv this side effect is not mentioned. Makes one wonder where the FDA is?

Anonymous said...

Where is the underfunded, over worked FDA? They are busy harassing certified, legal, safe raw dairy farmers and families with late night raids and interviews in California, that's where.

Jonah said...

The lung cancer rate was 4/6000 in users compared to 1/4000 control group. That's not a statistically significant difference; I would still be willing to use Exubera myself. My mother the accountant agrees that it's not statistically significant.
I mean, it's interesting and if they were going to keep it on the market, it'd be worth following up. But it's definitely not a strong enough correlation to be able to say, Exubera causes lung cancer.

Jenny said...

Actually, it is statistically significant, or Pfizer would not have had to announce it.

And though the number is low, if you personally are one of the "excess deaths" it is going to seem very significant indeed.

Putting a growth factor into your lung is probably not the smartest thing you can do. We know people get bad things happening in their SKIN when they inject in the same place all the time over a period of years--fatty overgrowth and scar tissue. No reason not to believe the same thing would happen if the lungs over time after overexposure to insulin.