What are the side effects of tirzepatide?

Side Effects of Tirzepatide

Gastrointestinal side effects are the most common adverse reactions to tirzepatide, affecting up to 49% of patients at the highest dose, with nausea (31%), diarrhea (23%), vomiting (12%), constipation (5%), and abdominal pain (5%) being the most frequently reported. 1

Common Side Effects

Gastrointestinal Effects

• Dose-dependent gastrointestinal adverse events occur in:
  • 39% of patients at 5 mg dose
  • 46% of patients at 10 mg dose
  • 49% of patients at 15 mg dose 2
• Most common specific GI effects:
  • Nausea (31%)
  • Diarrhea (23%)
  • Vomiting (12%)
  • Constipation (5%)
  • Abdominal pain (5%) 1

Other Common Side Effects

• Decreased appetite
• Injection site reactions (rare, <1% of patients) 1
• Mild hypoglycemia (blood glucose <70 mg/dL) - highest with 10 mg dose at 22.6% 2

Serious Side Effects

Rare but Serious Complications

• Acute pancreatitis (≤1%)
• Cholelithiasis (≤1%)
• Cholecystitis (≤1%)
• Severe hypoglycemia (≤1%) 2
• Appendicitis (rare, case reports exist) 3

Potentially Life-Threatening Complications

• Severe electrolyte disturbances secondary to prolonged GI side effects may lead to cardiac arrhythmias in rare cases 4
• Thyroid C-cell tumors (contraindicated in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2) 1

Management of Side Effects

Minimizing Gastrointestinal Effects

• Start with lower doses (2.5 mg weekly) and gradually titrate upward
• Follow standard dose escalation protocol:
  • 2.5 mg weekly for 4 weeks
  • Increase to 5 mg weekly at weeks 5-8
  • Further increases to 7.5 mg, 10 mg, 12.5 mg, and 15 mg at 4-week intervals as needed and tolerated 1
• Dietary modifications:
  • Reduce meal size
  • Limit alcohol and carbonated beverages
  • Avoid high-fat diets 1
• Symptomatic management:
  • Consider antiemetics (e.g., ondansetron) for significant nausea
  • Use loperamide for troublesome diarrhea 1

Monitoring Recommendations

• Assess patients 4 weeks after initiation to monitor side effects
• Consider dose reduction rather than discontinuation if benefits outweigh side effects
• Monitor for severe abdominal pain, persistent nausea/vomiting, and elevated lipase levels due to pancreatitis risk
• Monitor electrolytes in patients with severe or prolonged GI symptoms 1, 4

Special Considerations

Contraindications

• Personal or family history of medullary thyroid carcinoma
• Multiple endocrine neoplasia syndrome type 2 1

Precautions

• Stop at least one week before elective surgical procedures
• Not recommended during pregnancy or in women who may become pregnant
• Assess for history of pancreatitis and gallbladder disease before initiating 1
• No dose adjustment required in renal impairment, even in end-stage renal disease 1

Drug Discontinuation

• Discontinuation rates due to adverse events:
  • Highest with 15 mg dose (10%) 2
• Sudden discontinuation results in regain of 50-67% of weight loss within 1 year 1

Understanding these side effects and following proper titration protocols can significantly improve tolerability and adherence to tirzepatide therapy. The risk-benefit profile remains favorable for most patients with type 2 diabetes or obesity when properly managed.