Is Tirzepatide (a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist) associated with paresthesia?

Tirzepatide and Paresthesia

Tirzepatide has not been specifically associated with paresthesia in the current medical literature and guidelines, though it shares a similar side effect profile to GLP-1 receptor agonists with predominantly gastrointestinal adverse effects being most common.

Common Side Effects of Tirzepatide

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist approved for treatment of type 2 diabetes and obesity. The most frequently reported adverse effects include:

• Gastrointestinal side effects (nausea, vomiting, diarrhea, esophageal reflux) - these are the most common adverse events, occurring in 39-49% of patients depending on dose 1
• Injection site reactions 2
• Elevated heart rate 2
• Hypoglycemia (particularly at higher doses) 3

Adverse Event Profile Based on Clinical Evidence

A systematic review of tirzepatide's safety profile revealed:

• Gastrointestinal adverse events are dose-dependent, with higher rates at 15 mg (49%) compared to 5 mg (39%) 1
• Drug discontinuation due to adverse events was highest with the 15 mg dose (10%) 1
• Severe adverse events including acute pancreatitis, cholelithiasis, and cholecystitis were rare (≤1%) 1
• Hypoglycemia risk was elevated with tirzepatide 15 mg (pooled RR=3.83,95% CI [1.19-12.30]) 3

Important Safety Considerations

According to current diabetes care guidelines, tirzepatide carries several important safety considerations:

• Pancreatitis has been reported in clinical trials, though causality has not been established 2
• Use caution in people with kidney disease when initiating or increasing dose due to potential risk of acute kidney injury 2
• May cause cholelithiasis and gallstone-related complications 2
• Gastrointestinal disorders (severe constipation and small bowel obstruction/ileus progression) 2
• Monitor for potential consequences of delayed absorption of oral medications 2
• Black box warning: Risk of thyroid C-cell tumors in rodents (human relevance not determined) 2

Neurological Effects

While paresthesia is not specifically listed as a common side effect of tirzepatide in the current guidelines:

• GLP-1 receptors are found in various parts of the central nervous system, including the hippocampus, neocortex, spinal cord, and cerebellum 2
• The primary neurological effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists like tirzepatide appear to be related to appetite regulation through action on receptors in the hypothalamus and brainstem nuclei 2

Clinical Implications

For clinicians prescribing tirzepatide:

• Start at a low dose and titrate upward slowly to minimize gastrointestinal side effects 2
• Monitor patients for potential drug interactions, particularly with medications that have a narrow therapeutic index 2
• Advise patients using oral hormonal contraception to use or add a non-oral contraception method for 4 weeks after initiation and dose escalations 2
• Be aware that discontinuation rates are higher with 10 mg and 15 mg doses compared to 5 mg 3

While paresthesia is not specifically mentioned in the current literature on tirzepatide, clinicians should monitor for and document any neurological symptoms in patients taking this medication, as post-marketing surveillance may reveal additional adverse effects not captured in clinical trials.