Adverse Effects of Mounjaro (Tirzepatide)
Most Common Adverse Effects
The most common adverse effects of Mounjaro are gastrointestinal in nature, occurring in ≥5% of patients: nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain. 1 These gastrointestinal side effects are typically most pronounced during dose escalation and may diminish over time. 2, 3
Gastrointestinal Effects by Frequency
- Nausea occurs in 17-22% of patients 4
- Diarrhea affects 13-16% of patients 4
- Vomiting occurs in 6-10% of patients 4
- Decreased appetite is reported in ≥5% of patients 1
- Constipation affects ≥5% of patients 1
- Dyspepsia and abdominal pain each occur in ≥5% of patients 1
Other Common Effects
- Injection site reactions can occur with subcutaneous administration 2
- Elevated heart rate has been observed in patients taking tirzepatide 2
Serious Adverse Events Requiring Immediate Action
Pancreatitis
Discontinue Mounjaro immediately if pancreatitis is suspected. 2, 3, 1 Pancreatitis has been reported in clinical trials, though causality has not been definitively established. 2 Look for severe abdominal pain that will not go away, with or without vomiting, potentially radiating from the abdomen to the back. 1
Acute Kidney Injury
Use extreme caution when initiating or increasing doses in patients with pre-existing kidney disease. 2, 3 Diarrhea, nausea, and vomiting may cause dehydration, which can precipitate or worsen kidney problems. 1 Monitor renal function closely in patients with renal impairment who report severe gastrointestinal reactions. 1
Gallbladder Disease
Monitor for cholelithiasis (gallstones) and gallstone-related complications, particularly in patients experiencing rapid weight loss. 2, 3 Acute gallbladder disease has occurred in clinical trials. 1 Evaluate patients reporting right upper quadrant pain, fever, yellowing of skin or eyes (jaundice), or clay-colored stools. 1
Severe Gastrointestinal Obstruction
Watch for severe constipation, small bowel obstruction, and ileus progression. 2, 3 Tirzepatide has not been studied in patients with severe gastrointestinal disease and is not recommended in these patients. 1 Patients with pre-existing gastrointestinal disorders require particularly careful monitoring. 3
Hypersensitivity Reactions
Discontinue Mounjaro immediately if serious hypersensitivity reactions occur. 1 Stop the medication and seek immediate medical attention if patients develop swelling of face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or dizziness, or very rapid heartbeat. 1
Hypoglycemia Risk
Tirzepatide carries a lower hypoglycemia risk compared to insulin therapy. 2, 3 The risk for hypoglycemia is higher when Mounjaro is used with insulin secretagogues (such as sulfonylureas) or insulin. 1 Tirzepatide probably reduces severe hypoglycemia compared to insulin (RR, 0.21 [CI, 0.11 to 0.38]). 2, 3
Signs of Hypoglycemia to Monitor
- Dizziness or light-headedness, sweating, confusion or drowsiness 1
- Headache, blurred vision, slurred speech 1
- Shakiness, fast heartbeat, anxiety, irritability, or mood changes 1
- Hunger, weakness, feeling jittery 1
Reduce the dose of insulin secretagogues or insulin when initiating tirzepatide to minimize hypoglycemia risk. 1
Black Box Warning and Contraindications
Thyroid C-Cell Tumors
Mounjaro carries an FDA black box warning for risk of thyroid C-cell tumors observed in rodents, though human relevance has not been determined. 2, 3, 1 The medication is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. 3, 1
Special Monitoring Considerations
Diabetic Retinopathy
Monitor patients with a history of diabetic retinopathy for progression. 1 Tirzepatide has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. 1
Drug Absorption and Interactions
Tirzepatide delays gastric emptying and may impact absorption of concomitantly administered oral medications. 1 This is particularly concerning for medications with narrow therapeutic indices like warfarin. 2, 3 Monitor effects of oral medications with narrow therapeutic index closely. 2
Contraception Considerations
Women using oral hormonal contraception must use or add a non-oral contraceptive method for 4 weeks after initiation and for 4 weeks after each dose escalation. 2, 3, 1 Tirzepatide may reduce the effectiveness of oral contraceptives due to delayed gastric emptying. 3
Perioperative Risk
Instruct patients to inform healthcare providers of any planned surgeries or procedures. 1 Pulmonary aspiration during general anesthesia or deep sedation has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries. 1
Comparative Safety Profile
Tirzepatide may have a higher rate of certain adverse events compared to GLP-1 agonists alone. 3 GLP-1 agonists probably reduce serious adverse events compared with tirzepatide (RR, 0.57 [CI, 0.34 to 0.96]). 2, 3 However, tirzepatide may reduce serious adverse events compared with insulin (RR, 0.80 [CI, 0.67 to 0.96]). 2, 3
Overall, tirzepatide does not differ from usual care for serious adverse events (RR, 0.79 [CI, 0.51 to 1.22]). 2
Practical Management Strategies
Dose Titration
Gradual dose titration is essential to minimize gastrointestinal side effects. 3 Start at 2.5 mg subcutaneously once weekly, increase to 5 mg after 4 weeks, then increase in 2.5 mg increments after at least 4 weeks on the current dose if additional glycemic control is needed. 1
Hydration
Ensure adequate fluid intake to reduce the risk of dehydration-related complications, particularly acute kidney injury. 1 This is especially important for patients experiencing gastrointestinal side effects.
Storage and Handling
Store in refrigerator between 36°F to 46°F (2°C to 8°C), or at room temperature up to 86°F (30°C) for up to 21 days. 1 Do not freeze or use if frozen. 1