Mounjaro (Tirzepatide) Side Effects
Mounjaro causes primarily gastrointestinal side effects—nausea, vomiting, diarrhea, and esophageal reflux—which are the most common adverse events, along with injection site reactions and elevated heart rate. 1
Common Side Effects
Gastrointestinal Effects (Most Frequent)
- Nausea occurs in approximately 13-31% of patients, representing the most common adverse event 1, 2
- Diarrhea affects 12-23% of patients 1, 2
- Vomiting occurs in 12-18% of patients 2
- Constipation develops in approximately 5% of patients 2
- Esophageal reflux is commonly reported 1
- These gastrointestinal symptoms typically abate over time with continued use 1
Other Common Effects
- Injection site reactions occur frequently 1
- Elevated heart rate is a recognized side effect requiring monitoring 1
- Hypoglycemia can occur, particularly when combined with insulin or insulin secretagogues, though the risk is low when used without these agents 1, 3
- Decreased appetite is common 4
Serious Safety Concerns
Pancreatitis
- Pancreatitis has been reported in clinical trials, though causality has not been established 1
- Discontinue tirzepatide immediately if pancreatitis is suspected 1
Kidney-Related Risks
- Use caution in patients with kidney disease when initiating or increasing doses due to potential risk of acute kidney injury 1
- This risk is particularly relevant given the gastrointestinal side effects that can lead to dehydration 1
Gallbladder Disease
- May cause cholelithiasis (gallstones) and gallstone-related complications 1
Gastrointestinal Obstruction
- Severe gastrointestinal disorders including severe constipation, small bowel obstruction, and ileus progression have been reported 1
Electrolyte Disturbances and Cardiac Arrhythmias
- Severe vomiting and diarrhea can lead to profound electrolyte imbalances (hypokalemia, hypomagnesemia, hypocalcemia) that may precipitate life-threatening ventricular arrhythmias, including ventricular fibrillation 5
- Vigilant electrolyte monitoring is crucial, particularly in patients on high doses (15 mg) or those with additional risk factors 5
- Consider beta blockers if symptomatic cardiac arrhythmias or tachycardia develop 2
Black Box Warning
- Risk of thyroid C-cell tumors in rodents; human relevance has not been determined 1
Drug Interactions and Special Considerations
Oral Medication Absorption
- Monitor effects of oral medications with narrow therapeutic index (such as warfarin) or whose efficacy depends on threshold concentration 1
- Tirzepatide slows gastric emptying, which may affect absorption of oral medications 1
Oral Contraceptives
- Advise patients using oral hormonal contraception to use or add a non-oral contraception method for 4 weeks after initiation and after each dose escalation 1
Dose-Dependent Considerations
- Higher doses (15 mg) are associated with increased frequency of gastrointestinal side effects 6
- Treatment discontinuation rates increase with higher doses: 10% at 5 mg, 12% at 10 mg, and 18% at 15 mg compared to 3% with placebo 6
Clinical Context
The safety profile of tirzepatide is generally consistent with the GLP-1 receptor agonist class, with most adverse events being mild to moderate in severity 4, 3. The gastrointestinal side effects, while common, typically improve with continued use 1. However, the potential for severe electrolyte disturbances leading to life-threatening arrhythmias, particularly at higher doses, represents a previously undocumented risk that requires clinical vigilance 5.