Side Effects of Tirzepatide
Gastrointestinal side effects are the most common adverse reactions to tirzepatide, with nausea affecting up to 31% of patients, diarrhea 23%, vomiting 12%, constipation 5%, and abdominal pain 5%. 1
Common Adverse Effects
Gastrointestinal Effects
Dose-dependent gastrointestinal side effects occur in 39-49% of patients 2:
- Nausea (31%)
- Diarrhea (23%)
- Vomiting (12%)
- Constipation (5%)
- Abdominal pain (5%)
- Dyspepsia
- Gastrointestinal reflux
The incidence increases with higher doses:
- 39% at 5 mg dose
- 46% at 10 mg dose
- 49% at 15 mg dose 2
Other Common Side Effects
- Injection site reactions (rare, <1%) 1
- Increased heart rate 1
- Mild hypoglycemia (blood glucose <70 mg/dL) - highest with 10 mg dose (22.6%) 2
Serious Adverse Effects (Rare)
- Severe gastrointestinal disorders, including intestinal obstruction 1
- Potential risk of acute kidney injury, particularly when initiating or increasing dose in patients with renal disease 1
- Black box warning: Risk of thyroid C-cell tumors in rodents (human relevance not determined) 3, 1
- Rates of fatal adverse events, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis are extremely low (≤1%) 2
Management of Side Effects
Dose Titration
- Start at lower doses and titrate upward slowly to minimize gastrointestinal effects 3
- Consider dose reduction rather than discontinuation if benefits outweigh side effects 1
Gastrointestinal Side Effects Management
- For nausea: Consider antiemetics like ondansetron before tirzepatide dose 1
- For constipation: Increase fiber intake, ensure adequate hydration, consider mild laxatives 1
- For diarrhea: Use loperamide as needed and ensure electrolyte replacement 1
- Reduce meal size 3
- Limit alcohol and carbonated drinks 3
- Avoid high-fat diet 3
Special Considerations
Surgical Considerations
- Stop weekly tirzepatide injections at least one week before elective procedures to minimize aspiration risk due to delayed gastric emptying 1
- Consult with anesthesiologist before any surgical procedure 1
Contraindications
- Personal or family history of medullary thyroid carcinoma 1
- Multiple endocrine neoplasia syndrome type 2 1
- Pregnancy or women who may become pregnant 3
Discontinuation Rates
- Drug discontinuation due to adverse events is highest with the 15 mg dose (10%) 2
- Tirzepatide 10 mg and 15 mg are associated with higher discontinuation rates compared to 5 mg 4
Monitoring Recommendations
- Regular follow-up to assess side effect burden and medication efficacy 1
- Monitor for weight loss and glycemic control as expected benefits 1
- Be aware that most adverse effects are mild to moderate in severity, with severe adverse events being rare 1
Understanding these side effects and implementing appropriate management strategies can help optimize patient outcomes while minimizing adverse reactions when using tirzepatide.