Can Mounjaro (tirzepatide) cause neuropathy?

Can Mounjaro (Tirzepatide) Cause Neuropathy?

Mounjaro (tirzepatide) does not directly cause peripheral neuropathy, but rapid weight loss associated with its use can lead to compression neuropathies, particularly peroneal nerve compression causing foot drop—a phenomenon known as "slimmer's paralysis." 1, 2

Direct Neuropathy Risk

• Tirzepatide is not listed among medications that directly cause peripheral neuropathy, unlike chemotherapeutic agents (vincristine, oxaliplatin, paclitaxel, bortezomib, thalidomide) or certain antiretrovirals that have established neurotoxic mechanisms 3
• The drug's mechanism as a dual GLP-1/GIP receptor agonist does not involve direct neurotoxic effects 4, 5
• In animal studies, tirzepatide actually demonstrated neuroprotective properties by modulating insulin resistance and inflammatory pathways in diabetic rats 6

Indirect Neuropathy Risk: Slimmer's Paralysis

• Two documented cases showed patients developing bilateral foot drop within 6-8 months of starting tirzepatide due to peroneal nerve compression from rapid weight loss 1
• A retrospective observational study identified common peroneal neuropathy causing foot drop as an adverse event not mentioned in the drug's prescribing information 2
• This compression neuropathy occurs when rapid fat loss removes protective cushioning around superficial nerves, particularly the peroneal nerve at the fibular head 1

Timing and Monitoring

• Most adverse drug reactions to tirzepatide occur within 1-6 months of initiation, with the highest frequency at the 2.5-5 mg dose range 2
• Enhanced monitoring is warranted for patients experiencing rapid weight loss, as this is the primary risk factor for compression neuropathy 2
• Baseline neurological evaluation before initiating therapy is not standard for tirzepatide (unlike neurotoxic chemotherapy), but awareness of this complication is essential 1

Clinical Presentation

• Slimmer's paralysis presents as foot drop (inability to dorsiflex the foot), typically bilateral, developing over weeks to months during active weight loss 1
• This differs from diabetic neuropathy, which presents as symmetric "glove and stocking" distribution with primarily sensory symptoms and gradual onset 3
• Pre-existing diabetic neuropathy is not a contraindication to tirzepatide use, as the drug may actually improve glycemic control and slow neuropathy progression through better diabetes management 7, 4

Management Approach

• If foot drop or other focal neuropathy develops during tirzepatide therapy, consider dose reduction or temporary discontinuation while evaluating for nerve compression 1, 2
• Physical therapy and ankle-foot orthoses may be necessary for peroneal nerve palsy 1
• Continue optimizing glucose control, as this remains the primary intervention for preventing diabetic neuropathy progression 7, 8

Key Distinction

The critical distinction is that tirzepatide does not cause the toxic, length-dependent, symmetric peripheral neuropathy seen with chemotherapy agents or the metabolic neuropathy from diabetes itself—rather, it creates a mechanical risk through rapid body composition changes 1, 2.