Common Adverse Effects of Tirzepatide
Gastrointestinal side effects are the most common adverse effects of tirzepatide, with nausea, diarrhea, and decreased appetite being particularly prevalent and dose-dependent. 1, 2
Gastrointestinal Side Effects
- Nausea is one of the most frequent gastrointestinal adverse effects, occurring in a dose-dependent manner 2
- Diarrhea is commonly reported across all doses of tirzepatide 2, 3
- Vomiting occurs more frequently with higher doses 3
- Constipation can develop during treatment 1, 3
- Decreased appetite is significantly higher with tirzepatide compared to placebo and insulin 3
- Dyspepsia (indigestion) and gastroesophageal reflux may occur during treatment 1
- Abdominal pain may be experienced by some patients 2
Incidence and Dose Relationship
- Gastrointestinal adverse effects show a clear dose-dependent relationship: 39% with 5 mg, 46% with 10 mg, and 49% with 15 mg 2
- Nausea, vomiting, and diarrhea specifically show dose-dependent increases in frequency 3, 4
- Gastrointestinal side effects typically occur during the initial stages of treatment and tend to diminish over time 3
Other Common Adverse Effects
- Delayed gastric emptying due to GLP-1 receptor activation, which can affect medication absorption 1
- Increased heart rate/tachycardia may occur in some patients 5, 1
- Risk of hypoglycemia, particularly when combined with insulin or insulin secretagogues 1, 4
- Injection site reactions, which increase with higher doses 4
Management of Adverse Effects
- Start tirzepatide at a low dose and titrate upward slowly to minimize gastrointestinal symptoms 5
- Reduce meal size to help manage gastrointestinal symptoms 5
- Limit alcohol and carbonated drinks to reduce reflux symptoms 5
- Avoid high-fat diets to help minimize constipation 5
- Monitor for cardiac symptoms; if tachycardia becomes symptomatic, consider beta blockers 5
- Avoid use in patients with gastroparesis due to the risk of worsening delayed gastric emptying 5
Rare but Important Adverse Effects
- Gallbladder disorders can occur but are usually asymptomatic 5
- Acute pancreatitis is rare (≤1%) across all doses 2
- Cholelithiasis and cholecystitis are extremely rare (≤1%) 2
- Fatal adverse events are very rare (≤1%) 2
Discontinuation Rates
- Drug discontinuation due to adverse effects is highest with the 15 mg dose (approximately 10%) 2
- Tirzepatide 10 mg and 15 mg are associated with higher discontinuation rates compared to the 5 mg dose 4
Special Considerations
- In the perioperative period, tirzepatide's effect on delayed gastric emptying should be considered when planning procedures requiring general anesthesia 1
- The gastrointestinal adverse effects profile of tirzepatide is generally similar to that of GLP-1 receptor agonists, though some studies suggest higher rates of certain symptoms 3, 6