What are the side effects of Mounjaro (tirzepatide)?

Side Effects of Mounjaro (Tirzepatide)

Gastrointestinal side effects are the most common adverse reactions to Mounjaro (tirzepatide), occurring in 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

• Nausea: Affects approximately 31% of patients
• Diarrhea: Occurs in about 23% of patients
• Vomiting: Reported by 12% of patients
• Constipation: Experienced by 5% of patients
• Abdominal pain: Affects 5% of patients 1

These gastrointestinal side effects are typically:

• Dose-dependent (increasing with higher doses)
• More common during initiation and dose escalation
• Mild to moderate in severity 2
• Similar to those seen with GLP-1 receptor agonists 3

Other Common Side Effects

• Decreased appetite
• Injection site reactions (rare, <1%) 1
• Mild hypoglycemia (blood glucose <70 mg/dL), particularly with the 10 mg dose (22.6%) 2

Management of Gastrointestinal Side Effects

To minimize gastrointestinal effects:

1. Follow proper dose titration (starting at 2.5 mg weekly with gradual increases)
2. Reduce meal size
3. Limit alcohol and carbonated beverages
4. Avoid high-fat diets
5. Consider antiemetics (e.g., ondansetron) for significant nausea
6. Use loperamide for troublesome diarrhea 1

Serious but Rare Side Effects

Acute Pancreatitis

• Very rare (≤1% incidence) 2
• Monitor for severe abdominal pain, persistent nausea/vomiting, and elevated lipase levels 1, 4

Other Serious Concerns

• Risk of medullary thyroid carcinoma (contraindicated in patients with personal/family history of MTC or MEN2) 1
• Drug discontinuation due to adverse events (highest with 15 mg dose at 10%) 2
• Severe hypoglycemia (extremely rare, ≤1%) 2
• Cholelithiasis and cholecystitis (extremely rare, ≤1%) 2

Special Considerations

Drug Interactions

• When used with insulin or insulin secretagogues (sulfonylureas, glinides), dose adjustments may be needed to prevent hypoglycemia 1
• Medications that increase GI motility may reduce tirzepatide absorption 1
• Oral medications should be taken at least 1 hour before tirzepatide injection when possible 1

Contraindications and Precautions

• Contraindicated in patients with personal/family history of medullary thyroid carcinoma or MEN2 syndrome
• Not recommended during pregnancy or in women who may become pregnant
• Should be stopped at least one week before elective surgical procedures 1

Monitoring Recommendations

• Follow-up 4 weeks after initiation to assess side effects and response
• Monitor for severe abdominal pain, persistent nausea/vomiting (pancreatitis risk)
• Consider dose reduction rather than discontinuation if benefits outweigh side effects
• More frequent glucose monitoring when starting or stopping potentially interacting medications 1

Clinical Pearls

• Side effects are typically more pronounced during initiation and dose escalation
• Proper dose titration is crucial for minimizing adverse effects
• Most gastrointestinal side effects improve over time with continued treatment
• The safety profile is generally consistent with that of GLP-1 receptor agonists 3
• Sudden discontinuation results in regain of 50-67% of weight loss within 1 year 1