From the Guidelines
Tirzepatide is associated with common adverse reactions including nausea, diarrhea, vomiting, constipation, and abdominal pain, which are dose-dependent and can be managed with slow titration and hydration. According to the most recent study published in JAMA in 2023 1, the most common adverse effects of tirzepatide are nausea (10%), diarrhea (7%), vomiting (2%), constipation (3%), and abdominal pain (3%). These gastrointestinal side effects are related to tirzepatide's mechanism of action as a GLP-1 and GIP receptor agonist, which slows gastric emptying and affects gut motility.
Other common adverse reactions include decreased appetite, dyspepsia, fatigue, dizziness, and gastroesophageal reflux disease. Some patients may experience hypoglycemia, particularly when tirzepatide is used in combination with insulin or insulin secretagogues. Injection site reactions can occur but are generally mild. Less common but important adverse effects include pancreatitis, gallbladder disease, and hypersensitivity reactions.
The management of these adverse effects can be guided by the recommendations outlined in the Anaesthesia study published in 2024 1, which suggests that slow titration, hydration, and dietary adjustments can help minimize gastrointestinal symptoms. Patients should be advised to stay well-hydrated and consider smaller, more frequent meals to help manage gastrointestinal symptoms.
Key points to consider when managing tirzepatide-related adverse reactions include:
- Starting with a low dose and gradually increasing it according to the prescribed titration schedule
- Staying well-hydrated to minimize gastrointestinal symptoms
- Considering smaller, more frequent meals to help manage gastrointestinal symptoms
- Monitoring for signs of hypoglycemia, particularly when used in combination with insulin or insulin secretagogues
- Being aware of the potential for less common but important adverse effects such as pancreatitis, gallbladder disease, and hypersensitivity reactions.
From the FDA Drug Label
The following serious adverse reactions are described below or elsewhere in the prescribing information: In the pool of placebo-controlled trials, severe gastrointestinal adverse reactions occurred more frequently among patients receiving MOUNJARO (5 mg 1.3%, 10 mg 0.4%, 15 mg 1.2%) than placebo (0. 9%). Hypersensitivity reactions have been reported with MOUNJARO in the pool of placebo-controlled trials, sometimes severe (e.g., urticaria and eczema); hypersensitivity reactions were reported in 3. 2% of MOUNJARO-treated patients compared to 1.7% of placebo-treated patients. Injection Site Reactions In the pool of placebo-controlled trials, injection site reactions were reported in 3.2% of MOUNJARO-treated patients compared to 0.4% of placebo-treated patients. Acute Gallbladder Disease In the pool of placebo-controlled clinical trials, acute gallbladder disease (cholelithiasis, biliary colic and cholecystectomy) was reported by 0. 6% of MOUNJARO-treated patients and 0% of placebo-treated patients. Dysesthesia In the pool of placebo-controlled clinical trials, dysesthesia was reported by 0.4%, 0.4%, and 0.4% of patients treated with MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. Dysgeusia In the pool of placebo-controlled clinical trials, dysgeusia was reported by 0. 1% of MOUNJARO-treated patients and 0% of placebo-treated patients. Laboratory Abnormalities Amylase and Lipase Increase In the pool of placebo-controlled clinical trials, treatment with MOUNJARO resulted in mean increases from baseline in serum pancreatic amylase concentrations of 33% to 38% and serum lipase concentrations of 31% to 42%
The common adverse reactions to tirzepatide include:
- Gastrointestinal adverse reactions: nausea, vomiting, diarrhea
- Hypersensitivity reactions: sometimes severe (e.g., urticaria and eczema)
- Injection site reactions
- Acute gallbladder disease (cholelithiasis, biliary colic and cholecystectomy)
- Dysesthesia
- Dysgeusia
- Laboratory abnormalities: increased amylase and lipase 2, 2, 2
From the Research
Common Adverse Reactions to Tirzepatide
The common adverse reactions to tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, are:
- Gastrointestinal (GI) adverse events, which are dose-dependent and include:
- Nausea
- Diarrhea
- Decreased appetite
- Vomiting
- Constipation
- Hypoglycemia (blood glucose < 70 mg/dL)
- Injection-site reaction
Incidence of Adverse Reactions
The incidence of adverse reactions to tirzepatide varies by dose:
- 5 mg dose: 39% (95% CI, 35%-43%) of patients experienced GI adverse events 3
- 10 mg dose: 46% (95% CI, 42%-49%) of patients experienced GI adverse events 3
- 15 mg dose: 49% (95% CI, 38%-60%) of patients experienced GI adverse events 3
- The incidence of hypoglycemia was highest with the 10 mg dose (22.6%) 3
- The incidence of nausea, diarrhea, and decreased appetite was dose-dependent and increased with higher doses of tirzepatide 4, 5, 6
Comparison to Other Medications
Tirzepatide has a similar safety profile to GLP-1 receptor agonists, except for a higher risk of hypoglycemia and discontinuation at higher doses 6