March 25, 2007

Does Januvia Slow Wound Healing? Does it Cause Cancer?

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.

Note to visitors in 2009:

This is a very old blog post. For the most recent information about Januvia's impact on cancers of the lung, prostate, ovary and melanoma, please visit this page:

Januvia

where you will find many links to journal research about the impact of DPP-4 and cancer in the section headed "Research Connecting DPP-4 and Cancer."

Below is the original post which was made on 3/25/2007:

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Now that I've taken Januvia for a few months and had a chance to do some more research on it, a couple of issues have come up that are making me rethink whether it is wise to take it, even though I am getting such good results.

My experience with Slow Wound Healing

After I'd been taking Januvia for a few weeks I cut myself (not very seriously) while cooking. But it seemed to take forever for the wound to heal. At the same time I noticed that I was getting sore spots on my fingers where I was testing my blood sugar. This really was unusual. I'd been testing 6-8 times a day while on insulin and my fingers never hurt. Suddenly they were getting red and sore.

This raised the concern for me that the slight alterations to the immune system, and possibly other effects of DDP-4 were affecting healing. I posted about this on the Januvia blog at http://diabetes.blog.com and someone chimed in that they had also noticed slow wound healing which went away when they stopped the Januvia.

This could be a VERY serious concern, especially if you were to have surgery while taking this drug. I asked a surgeon about this when I was considering some elective surgery, and she told me that I'd have to ask my endocrinologist because she prescribed the drug. However, my endo knows only what is in the prescribing information, which doesn't mention any effect on the immune system except that Januvia makes some minor changes in white blood cell levels the importance of which is unknown. (How's that for avoiding the issue. Why isn't it known?)

The relevant data about how DPP-4 inhibition affects the immune system is hidden in scholarly studies of the effects of inhibiting DPP-4 which make it clear that DPP-4 inhibition does weaken immune response. I think, though my understanding of molecular biology isn't strong enough to be sure, that DPP-4 inhibition may have some effect on the process of healing itself.

If you've experienced any wound healing problems with Januvia, please contact me. Click on my profile and use the email address there, rather than posting a comment, if you want a reply.

Could Januvia Promote Cancer?

Because suppressing DPP-4 weakens the immune system, I have another very serious concern about whether it might promote cancer. DPP4 is also suppressed by melanoma cells and prostate cancer cells, and it is speculated that this might be what allows these tumors to fend off the immune system cells that are supposed to kill them. Rats fed a very high dose of Januvia (60 times the normal amount) did develop liver cancer, though mice did not. This is not trivial and only a lot of time will reveal the impact of DPP4 suppression on people.

I have seen it argued that since Januvia turns down the immune system, it might be extremely useful for people with diabetes who have inflammatory conditions like artery disease, gum disease, arthritis, and of course, inflammation of the beta cells. This may be true. Since inflammation is supposed to be what leads to heart attacks, downregulation of inflammation in the arteries could be good. It's also true that inflammation in the beta cells may be part of what kills them in Type 2 diabetes. There are also some initial studies showing that DPP-4 inhibition helps with autoimmune rheumatoid arthritis. However, for those of us who do not have inflammatory conditions--as revealed by tests like CRP (C-Reactive Protein), SED rate, etc.-- turning down the immune system might allow the random cancer cells we all produce from time to time to avoid detection and destruction.

Since I'm a melanoma survivor, I'm NOT happy about electively suppressing the same enzyme DPP-4 that melanoma cells suppress.

In an ideal world, we could trust the drug companies to test these drugs in ways that would assure us we weren't going to wake up in ten years and find out that this wonder drug increased our chances of getting cancer ten times. But this is a pill that retails for $5 a pill, sold by a drug company that really needs some new blockbuster drugs to keep its billion dollar profits going. They hit the market first with their oral incretin hormone pill which gives them a huge sales advantage. How likely are they to study the possibility that their fancy new drug has a fatal side effect that takes ten years to develop? The longest test of Januvia lasted just shy of two years.

I'm thinking I might talk to my doctor about switching to Byetta now that I know that incretin drugs are very effective for me. Byetta does not suppress enzymes and shouldn't have any direct effect on the immune system. (But then there is the concern about creating antibodies since it's injected. There's always something . . .)

NEW INFORMATION ABOUT JANUVIA AND CANCER
added September/2008:

http://diabetesupdate.blogspot.com/2008/09/more-evidence-connects-januvia-to.html

12 comments:

Jenny said...

Since posting this several people have chimed in on the Januvia blog at http://diabetes.blog.com/1162417/?page=last&msgsuccess=1#cmts.

So far they report: significant changes in CBC, problems healing gum disease that were improved by stopping Januvia (this reported by a nurse), pinkeye after starting Januvia.

Of course, all these will be dismissed by the manufacturer as "anectdotal" which they are.

But given the mechanism behind how Januvia works, these anecdotal responses should be taken seriously.

Bottom line DO NOT take Januvia before surgery of any kind until this issue is better understood.

Jenny said...

After some more research and a helpful email from a researcher who sent me some publications about Januvia not available on the web, it appears that wound healing itself may not be a problem. However, more inflammation while healing wounds may be. That is because another function off DPP-4 as a protease is to get rid of cytokines, which are what cause inflammation.

The function of DPP-4 in laying down fibers for healing appears to use DPP-4 as an enzyme, not a protease, and hence it isn't inhibited.

The question of the impact of DPP-4 suppression on melanoma, is not one to which there is currently an answer. We'll know after many thousands of people have taken the drug for a decade or more.

A key may to be to dose a DPP-4 inhibitor drug so that it wears off and hence is truly reversible. In one paper I was sent, the suggestion is made that the best DPP-4 inhibitor drug would be a very short acting one that lasted only for a few hours after eating because that is the only time that it affects GLP-1.

I'll be keeping my eye on the new DPP-4 drugs coming along, like Galvus, and would prefer one that wore off faster than Januvia does. Januvia has a half life of 12 hours (half is out of the system by then, but the other half takes a whole week to be totally gone, according to the Prescribing Information and that pretty much meshes with how long it was until my blood sugar reverted back.

OTOH, my blood sugar is a bit better now than when I started the Januvia, suggesting that it did have a positive effect on the beta cells.

Ralph said...

Hello Jenny,

I started Januvia yesterday 100mg daily.

I have been reading your blog and I am thankful that you and others are around to help all of us.

I am newly diagnosed as of 3/7/07 as a T2 diabetic. I should have been diagnosed about 1 1/2 years ago.

I will keep you posted on my experience. I am already seeing positive results. My numbers finally dropped under 100 into the 90s after one day. I was hovering 100-110.

Additionally, I take Meformin extended realease 1000mg in the AM and a 1000mg in the PM.

Charles said...

Prior to taking Januvia I had non-healing small sores on my upper arms and above my clavicles. These sores are no more than 1/4" and seem to come and go. I have never had a sore at any other spot.

Within 3 weeks of beginning a course of Januvia treatment I have developed a very different type of open wound (sore) on two places on the top of my left foot. Both are bothersome and despite applying 3-in-1 antibiotic are not healing.

jacqui said...

HI Jenny

I was diagnosed about 2 years ago and went on Metformin, then months later Actos. My doctor switched me to Januvia about a week ago.

I have had runny nose, sore throat and diahrrea. anyone else? and did it stop after a while?

nervous about staying on it, but hat ethe effects of actos.

Anonymous said...

Question: Has any one experienced extreme fatigue while taking Januvia? I've been taking this now for a year and suddenly(last couple of months) I'm very tired and my BS is steadly on the rise with both Januvia as well as inslin.
Thanks 2 Bears

Anonymous said...

I am a T1. Diagnosed at 43. They put me on insulin which proceeded to kill me 4 days later. I took matters into my own hands. At diagnosis my BS was 610 and my A1C was 11.9 and I could not see (that is what led me to the dr). I changed my diet COMPLETELY. I weighed 125 at diagnosis and weigh 120 today. I take 100mg of Januvia every morning and wait 1 hour to eat. I exercise 1.5 to 2 hours every day. I eat somewhere between 100 and 175 carbs per day. My a1c today is 5.1. Januvia IS a beta cell regenerator. I've doubled my insulin output over 8 months. Once a month I run full labs to check everything. This disease CAN be solved with diet and exercise. I have NO would healing problems at all. I test 10 to 12 times per day. There are foods that I must avoid but that is very very simple compared to dying of a hypo (which I did). I am entering my 7th triathalon next month. This disease is more about abusing the small intestines and pancreas with toxic foods that people are willing to admit and or realize.
Thank
mk

Jenny said...

Anonymous,

It is very unlikely you are a true Type 1.

You may have a slow form of LADA and be in the "honeymoon" stage or one of the odder forms of MODY. Both are diagnosed in thin people your age.

There is no evidence that Januvia regenerates beta cells. It causes increased insulin secretion in people whose beta cells are still alive. For a while.

I am glad for you that it is working, but when it stops, I hope you will learn how to use insulin properly so you can avoid hypo--it sounds like your doctor did not get you the proper training.

Anonymous said...

Its intersting that they consider gum problem as anectdotal. Before I started taking Januvia I spent a lot of money and pain in getting my gum disease under control. I had surgery where they made my pockets smaller by cutting away the extra tissue that cause deeper pockets. For two years after the surgery my gums were great. I started to take Januvia and all of the sudden the deep pockets and bleeding returned. I used Januvia for 6 months and stopped. I had all kind of other crazy symptons under Januvia but the gum tissue now seems to be improving after stopping Januvia

Jenny said...

Anon 8:14,

PLEASE ask your doctor to report your problem with your gums to the FDAs Medwatch program.

If your doctor won't report it, you can report it yourself.

Unless people report side effects through this program the FDA rarely becomes aware of them. There is no serious attempt at tracking problems with drugs once they have been approved.

susan said...

I have severe back pain and stiffness after a couple of hours of sleep since taking Januvia. I take Januvia after dinner.

Could it be inflammation from the effects of Januvia?

Jenny said...

Back and joint pain can certainly be an effect of the Januvia. Since some people report joint pain after taking Januvia that doesn't go away, I would not keep taking it in the hope of not creating permanent damage.