Drug-induced PN due to tirzepatide

I have been experiencing peripheral neuropathy (PN) following the initiation of Mounjaro/Zepbound (tirzepatide) therapy. At lower doses, I did not experience any neuropathic symptoms; however, upon titration to the 10 mg dose, I began to develop significant PN. Initially, I attributed the symptoms to my pre-existing spondylitis and continued treatment.

After several months of persistent and progressively debilitating symptoms, I undertook a structured assessment, documenting the timing, severity, associated activities, dietary intake, and concurrent medications. This process revealed a clear temporal association between the worsening of neuropathic symptoms and the administration of tirzepatide.

Discontinuation of the medication resulted in a substantial improvement in symptoms, although complete resolution was not achieved. To further investigate whether excipients or preservatives might have contributed, I trialed a compounded formulation of tirzepatide. The recurrence of identical neuropathic symptoms with the compounded version supports the conclusion that the active pharmaceutical ingredient itself was the likely cause.

I did not think to try the compounded version of the drug -- excellent probe.

In my case, transitioning to semaglutide stopped the progression, although to the best of my knowledge, the damage caused up to that point is essentially irreversible. We'll both of us have to keep an eye out for future DIPN publications that may prove helpful!

I am currently experiencing this as well. It's awful! I now have drop foot in both feet. Trying to help has been beyond frustrating. Any advice would so be appreciated. Everything is getting worse. I stopped zepbound six weeks ago.

Hi @moddydammy, Welcome to Connect. Sorry to hear that you have drug induced neuropathy and now have developed drop foot in both feet. The Foundation for Peripheral Neuropathy has a list of different treatments if you haven't already seen them - https://www.foundationforpn.org/treatments/. Others have mentioned using orthotics to help with drop foot. Have you discussed it with your doctor or foot specialist to see if they may have any suggestions?

You have my complete sympathy, both for the symptoms and the challenges finding help for something that is as rare as non-oncological DIPN -- in my experience, no one really knows what to do about it. Although to be fair, pretty much no one knows what to do about oncological DIPN, either. I've got a running weekly JAMA search on DIPN, and it keeps coming up with essentially nothing of any use, arguing that it's even an unpromising study area. (A search for tirzepatide or semaglutide, however, produces dozens of results every week. None of which, of course, mention DIPN.) So completely agree with @johnbishop : about the only thing you can get from a neurologist is advice on how to keep it from getting worse (avoid vitamin B6, for example). Beyond that, this is a great forum for finding practical things you can do to just cope, like, for example, orthotics or shoes or socks.

Welcome to a very special club!

Thank you and yes we just recently discussed braces for my legs and feet.

I've been feeling strange zaps and zings in my left foot a bunch. Hurts but all of the sudden today I could lift my left foot slightly off the ground. This gives me hope! It's been 7 weeks since I've been off zepbound.

I am curious to find others that this is happening to and band together. Has anyone told the FDA? What about the company? I plan to file something with my doctor because it's becoming more and more clear that all of this is from zepbound.

@moddydammy, I'm not sure others have reported the side effects of the drug but you can report side effects through MedWatch - https://www.fda.gov/safety/medical-product-safety-information/medwatch-forms-fda-safety-reporting.

Just filled out Form 3500B and mailed it. Took a couple of hours, plus a consultation with the pharmacy to nail down some dates. I'll be curious to see if I hear from them, given their staffing issues. Nonetheless, I feel better having done my bit to help this problem be taken seriously. So thank you for the nudge, @johnbishop .

The option of withholding your personal information from the manufacturer was interesting. I have to say that I, personally, am not terrified that Eli Lilly will want to pursue their vengeance upon me, but if I were a professional in the medical community, I can see how that might be a valid concern.

I will be for sure reporting this all when I see my doctor soon. He told me he would help me. My neurosurgeon even found information concerning the link between that type of medication and neuropathy. I will scan the information and share with you all soon.