Objective:

We report a case series of peroneal neuropathy associated with GLP-1 agonist-induced weight loss to raise awareness of this complication to encourage preventive measures.   

Background:

GLP-1 agonists are widely used for weight loss, with FDA approval. They can induce rapid and significant weight loss, which is a well-recognized etiology of common peroneal neuropathy at the fibular head. The proposed mechanism is subcutaneous tissue loss, causing nerve compression and/or stretching. Common presentations include foot drop and lower extremity paresthesias, which can affect activities of daily living. This complication is currently not part of the package insert or in commercial media.  

Design/Methods:

We have retrospectively studied five patients evaluated in our institution from August to September 2025 for foot drop following GLP-1 agonist treatment, with rapid and significant weight loss.  

Results:

In our series, mean age is 58.2 years (range: 52-65). Four patients are men, and one is woman. Mean duration from GLP-1 agonist initiation to symptom onset is 219.8 days (range: 14-480). The mean weight loss is 40.0 pounds (range: 5-80), which is 20.9% (range: 3.4-25.8) of body weight loss. Foot drop is severe in all five patients, with tibialis anterior strength below 4/5 MRC on initial visits. All underwent nerve conduction study and electromyography with electrophysiologic evidence of common peroneal neuropathy at the fibular head. Three of them reported tendency to cross their legs. None had diabetes mellitus, trauma, or compressive lesions. All were managed conservatively, including physical therapy and orthosis.      

Conclusions:

To our knowledge, this is the largest series of peroneal neuropathy caused by GLP-1-agonist-induced weight loss.  Patients should be counseled regarding this complication prior to initiating these agents, so that they can take preventive measures, such as avoiding leg crossing or prolonged bent knee posture especially during air travel.