Drug-induced PN due to tirzepatide

Has anyone experienced neuropathy as a side effect with taking Zepbound. My neuropathy began two months after beginning Zepbound. I continued taking it because both my primary and neurologist told me that neuropathy is not a side effect of Zepbound. However, every time I take the shot, my symptoms seem to get worse.

Hello @finnj01,

I combined your discussion with an existing discussion titled:

"Drug-induced PN due to tirzepatide"
- https://connect.mayoclinic.org/discussion/drug-induced-pn-due-to-tirzepatide/

Here, you can meet @profjan, @rainyb91566, @save4forever.

Thank you..

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@finnj01 You have my sympathy -- if you have a chance to scroll through my earlier experiences, you will learn that it took me a long time to find a physician who understood that this is a known side effect of zepbound. It's just a really, really unlikely one, and is rare enough that reasonable experts can conclude that the apparent correlation does not mean causation.

Fortunately/unfortunately, none of these people can do anything about it that you cannot do for yourself -- I would love for someone who is reading this to prove me wrong, of course.

There are three possible underlying truths here: (1) they are right, and it's not the zepbound; (2) they are wrong, and the PN is zepbound dose-dependent; (3) they are wrong, and the PN is not zepbound dose-dependent. In the case of either (2) or (3), you have one of two possible situations on your hands: (a) the current damage is not permanent, and will go away if you eliminate the cause; (b) the current damage is permanent, and will stop progressing (get no better and no worse) if you eliminate the cause. I seem to be dealing with (2)(b).

Basically, the only way to figure this out is to change your drug consumption and monitor the impact it has on your PN. Your options are to reduce/increase the zepbound dose, switch to another weight-loss drug, or stop taking any weight-loss drugs. If your PN stays the same, gets worse, or gets better, you've learned what you need to know.

I started by gradually dropping the dosage of the zepbound, which stopped the PN progression. Because hope springs eternal, I then switched to ozempic to see if that would further improve things. It did not, but neither did it make the situation worse. (I also prefer the ozempic multi-pen, which lets me tailor my dosages better than the single-dose zepbound pen.) I could have taken the final step of dropping off weight-loss drugs altogether, and chose not to. If the PN starts progressing again, I'll revisit that decision, or perhaps switch to yet another drug.

I haven't poked at it recently, but back when I was going through this, there was very little data-driven guidance concerning how best to stop zepbound or switch from one drug to another. The advice seemed to be to ramp down to the lowest dose of zepbound before stopping it, and then start ramping up the new drug beginning with the lowest dosage normally prescribed of that new drug. This seems sensible on its face, but I'm guessing it's mostly just what anyone would suggest for any drug, and not based on any zepbound-specific evidence.

As far as I know, there are no treatments that cure PN once the nerve damage has become permanent. Lots of people try lots of things to help manage specific symptoms, all of which seem to work for some people and not for others. It's worth wading into these if/when you are ready.

Thank you for responding. I truly believe now that it is from the Zepbound. I found that the stronger dose I took, the worse the pain was. I’m going to stop taking it and see if the pain subsides or lessens, which I’m hoping it will. I only wish my doctor had originally prescribed Ozempic which I had asked for and I wouldn’t be in this situation, but too late now. I will however show these posts to my doctors so that they know the possible PN side effects of Zepbound other than the ones they inform us about.

I took Mounjaro for 10 months and was diagnosed with small-fiber PN. I think doctors will eventually start linking more PN cases to tirzepatide. I am now extremely hesitant to take any GLP-1 types of meds.

@tripletb I took Zepbound 2.5mg x 3 doses. Developed severe not moderate pain in Right hand middle/ring finger occasionally radiating up to elbow. Also c/o moderate to mild pai- middle ring. finger in land hand with tingling sensation in those 2 fingers. EMG/NCV Results-Negative for large fiber peripheral neuropathy. Seen by Neurologist and was diagnosed by symptoms & not test results as having Idiopathic (?)Peripheral Neuropathy & Carpal Tunnel Syndrome!!

@save4forever Sounds plausible. Idiopathic would be a normal diagnosis by most practitioners after large fiber (and small fiber -- did anyone recommend testing for that?) has been ruled out, and it could happen in combination with carpal tunnel, although I'd be pretty amazed if the carpal tunnel were due to the zepbound. What are you planning to do next?

@projfan I’m experiencing something similar. Why do you believe the damage caused until this point is essentially irreversible? Is this based on your experience, or something you’ve read? Thank you.

@thebugshort Good question. I've found no indication in the medical literature of a path to reversing DIPN, although to be fair, almost all DIPN research that's published seems to concern cancer drugs, and no one seems to think that DIPN is a reason to withdraw the drugs -- all the work is about minimizing the drug side effects, not reversing them. If you find anything, I would love to see it.

I personally found that reducing dosages stopped the progression but failed to reverse the DIPN, and that switching forms of the drug after achieving a low maintenance dose made no difference. My neuropathy has now been stable for well over a year. It is possible that going off the drugs entirely rather that moving to a minimum dose would have worked, but I prefer the stabilized DIPN symptoms over knee replacement surgery -- I know better than to believe dropping the drugs and keeping the weight off using other means is a viable option for me personally.

I vaguely recall digging into the literature at the time concerning healing of the nerves after removing any stimulus driving PN, and finding nothing. Again, if you find any relevant studies, I'd be very interested in hearing about them.

In general, PN does not seem to be curable -- treatments seem to be focused on managing and reducing the symptoms, not on fixing the underlying problem.

Finally, although I have an automated search running in PubMed every week for DIPN, it's been months since I last dug elsewhere into this topic, so my reply here is based on aging data. The PubMed search has popped nothing of any use for a long time -- pretty much all of the work has been narrowly focused in ways that make it irrelevant to our specific problem. And if you look at the analyses of GLP-1 RA side effects, both beneficial and not, our problem barely emerges from the data at a population level. So really, what motivation does anyone have to go after it?