Can Zepbound (tirzepatide) cause paresthesia (tingling of the nerves)?

Paresthesia (Tingling) as a Side Effect of Zepbound (Tirzepatide)

Yes, Zepbound (tirzepatide) can cause paresthesia (tingling of the nerves) as a documented side effect. Paresthesia is specifically listed among the common side effects of tirzepatide in clinical guidelines.

Evidence for Paresthesia with Tirzepatide

• Paresthesia is explicitly mentioned as a common side effect of weight management medications in the 2025 American Diabetes Association Standards of Care, which includes tirzepatide (Zepbound) 1
• The combination medication phentermine/topiramate lists paresthesia as one of its most common side effects, and similar neurological effects have been observed with GLP-1/GIP receptor agonists like tirzepatide 1
• In the clinical guidelines for obesity management, paresthesia is included among the common adverse effects that patients may experience when taking weight loss medications 1

Mechanism and Clinical Significance

• Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works through multiple pathways that may affect neurological function 1
• The exact mechanism by which tirzepatide causes paresthesia is not fully elucidated, but it may be related to:
  • Metabolic changes affecting peripheral nerve function 1
  • Rapid weight loss potentially leading to nutritional deficiencies that affect nerve health 2
  • Possible effects on electrolyte balance that can influence nerve conduction 3

Management of Paresthesia

• If a patient experiences paresthesia while taking Zepbound, the following approach is recommended:
  • Assess the severity and distribution of the paresthesia 1
  • Consider dose reduction if symptoms are bothersome 1
  • Ensure adequate nutritional intake, particularly during rapid weight loss phases 2
  • Monitor for progression of symptoms that might indicate more serious neurological complications 2

Important Considerations and Warnings

• Recent case reports have documented more serious neurological adverse events associated with tirzepatide, including:

  • "Slimmer's paralysis" (foot drop due to peroneal nerve neuropathy) following rapid weight loss with tirzepatide 2
  • Rare but serious neurological complications such as autoimmune encephalitis 4
  • Rhabdomyolysis, which can present with muscle weakness and pain 5

• Patients should be advised to report persistent or worsening paresthesia, as it may require clinical evaluation to rule out more serious conditions 1, 2

Monitoring Recommendations

• Healthcare providers should:
  • Discuss the possibility of paresthesia with patients before starting Zepbound 1
  • Perform baseline neurological assessment 1
  • Follow up within 2-4 weeks of initiation to assess for side effects including paresthesia 6
  • Encourage resistance training and sufficient protein intake to minimize risk of neurological complications associated with rapid weight loss 1

Comparative Incidence

• While paresthesia is listed as a common side effect for tirzepatide, the incidence appears to be higher with certain other weight loss medications:
  • Phentermine/topiramate combination has a particularly high association with paresthesia 1
  • The exact comparative incidence of paresthesia between tirzepatide and other GLP-1 receptor agonists (like semaglutide) is not clearly established in the current guidelines 7

When prescribing Zepbound, healthcare providers should inform patients about the possibility of experiencing paresthesia and provide guidance on when to seek medical attention if these symptoms become concerning.