Tirzepatide-induced rapid weight loss linked to peroneal nerve palsy from leg crossing in two patients

Rapid weight loss can reduce protective adipose and muscle tissue around nerves, making them more susceptible to compression. Common peroneal nerve palsy, often termed 'slimmer's palsy,' is a recognized complication, frequently exacerbated by habitual postures like leg crossing. With the increasing use of potent weight loss medications such as tirzepatide, understanding and mitigating these risks becomes crucial. This addresses a gap in comprehensive patient counseling regarding potential iatrogenic injury during significant metabolic changes.

This case series describes 2 male patients who developed peroneal neuropathy during tirzepatide therapy for weight loss. Patient 1, a 55-year-old male, lost 50 pounds over 5 months. Patient 2, a 71-year-old male, lost 30 pounds over 3 months. Both patients habitually crossed their legs. The primary endpoint was the development of foot drop. Treatment involved behavioral modification to avoid leg crossing, physical therapy, and ankle bracing for Patient 1.

Both patients developed acute foot drop, with symptoms appearing over 24-72 hours. This neuropathy was attributed to compression of the peroneal nerve, exacerbated by the reduction of protective tissue around the nerve due to rapid weight loss. Patient 1 had severe hidradenitis suppurativa and was on immunosuppressants, while Patient 2 had insulin resistance. No other specific neurological deficits were reported. The cases highlight a direct temporal association between tirzepatide-induced weight loss, habitual leg crossing, and the onset of peroneal nerve palsy. Early recognition enabled timely intervention.

Resolution of foot drop signs occurred over 3 to 4 months in both patients following intervention.