Mounjaro (Tirzepatide) Side Effects
Gastrointestinal side effects are the most common adverse reactions with Mounjaro (tirzepatide), including nausea, vomiting, diarrhea, and decreased appetite, which are typically most pronounced during dose escalation and may diminish over time. 1, 2
Common Side Effects
- Gastrointestinal effects: Nausea (20-44%), diarrhea (16-32%), vomiting (7-25%), constipation (10-23%), and decreased appetite are the most frequently reported side effects and are dose-dependent 3, 1, 4
- Injection site reactions can occur with subcutaneous administration 3, 1
- Elevated heart rate has been observed in some patients 3, 1
- Hypoglycemia risk is present but generally lower than with insulin therapy, though the risk increases when used with insulin or sulfonylureas 2, 1
- Abdominal pain and indigestion (dyspepsia) are commonly reported 2, 5
Serious Adverse Events
- Pancreatitis: Stop using Mounjaro and seek immediate medical attention if you experience severe abdominal pain that may radiate to the back, with or without vomiting 3, 2
- Gallbladder problems: Tirzepatide may cause cholelithiasis (gallstones) and gallbladder-related complications, particularly with rapid weight loss 3, 1
- Gastrointestinal obstruction: Severe constipation, small bowel obstruction, and ileus progression have been reported, especially in patients with pre-existing gastrointestinal disease 3, 1
- Kidney problems: Acute kidney injury is a potential risk, particularly when initiating or increasing the dose in people with kidney disease 3, 1
- Thyroid C-cell tumors: The FDA label includes a black box warning regarding thyroid C-cell tumors observed in rodents, though human relevance has not been determined 3, 2
- Serious allergic reactions: Stop using Mounjaro and seek immediate medical help if you experience swelling of face/lips/tongue/throat, breathing problems, severe rash, or rapid heartbeat 2
Medication Interactions and Special Considerations
- Delayed oral medication absorption: Tirzepatide may delay absorption of oral medications, particularly concerning for medications with a narrow therapeutic index like warfarin 3, 1
- Hormonal contraception: Women using oral hormonal contraception should use or add a non-oral contraception method for 4 weeks after initiation and dose escalations 3, 1
- Electrolyte disturbances: Severe gastrointestinal side effects can lead to electrolyte imbalances, which in rare cases can be life-threatening 6
Risk Factors and Monitoring
- Dose-dependent side effects: Higher doses (10-15 mg) are associated with increased incidence of adverse events 4, 5
- Discontinuation rate: Approximately 10% of patients on the 15 mg dose discontinue treatment due to adverse events 4
- Gradual dose titration is essential to minimize gastrointestinal side effects 1
- Hydration is important, especially if taking insulin or sulfonylureas concurrently 1
Contraindications
- Personal or family history of medullary thyroid carcinoma 1, 2
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1, 2
- Previous serious allergic reaction to tirzepatide 2
Clinical Pearls
- Most gastrointestinal side effects are mild to moderate and tend to decrease over time with continued treatment 4, 5
- The incidence of severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis is extremely low (≤1%) across all doses 4
- Patients should be advised to report severe or persistent gastrointestinal symptoms, as these may require dose adjustment or discontinuation 2
- Tirzepatide should be discontinued if pancreatitis is suspected 3, 1
Tirzepatide offers significant benefits for glycemic control and weight loss, but proper patient selection, monitoring, and management of side effects are crucial for successful treatment outcomes 3, 7.