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Drug-induced PN due to tirzepatide

Posted by projfan @projfan, Mar 25 10:34am

Just a heads-up that sometimes, peripheral neuropathy can be traced to a new drug. Having gone through the usual tests, and finally landing in front of a hematologist for possible MGUS, I seem to have a definitive diagnosis. I don't have MGUS (apparently the test results were a false positive due to a recent infection). However, although he was not a neuropathy specialist, he does have lots of experience with drug-induced peripheral neuropathy, which is distressingly common when chemotherapy drugs are used.

After taking a thorough history to confirm the research he had done offline on my case, and doing a variety of physical checks, he concluded that the source of the problem was tirzepatide (zepbound). Apparently this is a known, low-probability (< 1%) side effect, although the mechanism causing it with this particular drug is unclear. This is not a problem with semaglutide (mounjovy or ozempic).

So if you already have symptoms of PN and are thinking about taking one of the new weight-loss drugs, I would really encourage you to avoid zepbound.

Interested in more discussions like this? Go to the Neuropathy Support Group.

rainyb91566 | @rainyb91566 | Apr 29 10:21am

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.

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projfan | @projfan | Apr 29 11:13am
In reply to @rainyb91566 "I have been experiencing peripheral neuropathy (PN) following the initiation of Mounjaro/Zepbound (tirzepatide) therapy. At lower..." + (show)
@rainyb91566

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.

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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!

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