What is the incidence of gastrointestinal (GI) symptoms with Mounjaro (tirzepatide)?

From the Guidelines

Gastrointestinal (GI) symptoms are common side effects of Mounjaro (tirzepatide), with the most recent and highest quality study suggesting that these symptoms can be mitigated with proper dosing and administration techniques. According to the most recent evidence from 1, the Dual GIP and GLP-1 RA (SQ) category, which includes Mounjaro, has a high incidence of GI side effects, including nausea, diarrhea, and vomiting. The study suggests that these symptoms can be managed by counseling patients on potential GI side effects, providing guidance on dietary modifications, and considering slower dose titration for those experiencing GI challenges.

Key GI Symptoms

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Abdominal pain

Management of GI Symptoms

• Start with the lowest dose (2.5 mg once weekly) and follow the recommended dose escalation schedule
• Take Mounjaro with small, low-fat meals
• Stay well-hydrated
• Avoid large meals
• Consider slower dose titration for those experiencing GI challenges
• Provide guidance on dietary modifications to mitigate GI side effects

Mechanism of Action

Mounjaro slows gastric emptying and affects gut hormone signaling as part of its mechanism of action as a GLP-1 and GIP receptor agonist, which can contribute to the development of GI symptoms. However, with proper management and administration, these symptoms can be minimized, and the benefits of Mounjaro can be maximized. As noted in 1, the Dual GIP and GLP-1 RA (SQ) category has a very high glucose-lowering efficacy and a high weight loss efficacy, making it a valuable treatment option for patients with type 2 diabetes.

From the FDA Drug Label

In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving MOUNJARO than placebo (placebo 20.4%, MOUNJARO 5 mg 37.1%, MOUNJARO 10 mg 39.6%, MOUNJARO 15 mg 43.6%). The following gastrointestinal adverse reactions were reported more frequently in MOUNJARO-treated patients than placebo-treated patients (frequencies listed, respectively, as: placebo; 5 mg; 10 mg; 15 mg):

• Nausea (4,12,15,18)
• Diarrhea (9,12,13,17)
• Decreased Appetite (1,5,10,11)
• Vomiting (2,5,9)
• Constipation (1,6,7)
• Dyspepsia (3,8,5)
• Abdominal Pain (4,6,5)
• Eructation (0.4%, 3.0%, 2.5%, 3.3%)
• Flatulence (0%, 1.3%, 2.5%, 2.9%)
• Gastroesophageal reflux disease (0.4%, 1.7%, 2.5%, 1.7%)
• Abdominal distension (0.4%, 0.4%, 2.9%, 0.8%)

The incidence of gastrointestinal (GI) symptoms with Mounjaro (tirzepatide) is as follows:

• Nausea: 12% to 18%
• Diarrhea: 12% to 17%
• Vomiting: 5% to 9%
• Constipation: 6% to 7%
• Dyspepsia: 5% to 8%
• Abdominal Pain: 5% to 6% Gastrointestinal adverse reactions occurred in 20.4% of placebo-treated patients and 37.1% to 43.6% of MOUNJARO-treated patients 2.

From the Research

Incidence of Gastrointestinal Symptoms with Mounjaro (Tirzepatide)

• The incidence of gastrointestinal (GI) symptoms with Mounjaro (tirzepatide) has been reported in several studies 3, 4, 5, 6, 7.
• Common GI symptoms associated with tirzepatide include nausea, diarrhea, vomiting, decreased appetite, dyspepsia, and constipation 4, 5, 6, 7.
• The incidence of these symptoms is dose-dependent, with higher doses of tirzepatide associated with a higher incidence of GI symptoms 5, 6.
• The incidence of nausea with tirzepatide has been reported to be around 20.43% 4, while the incidence of diarrhea has been reported to be around 16.24% 4.
• The incidence of vomiting with tirzepatide has been reported to be around 9.05% 4, while the incidence of decreased appetite has been reported to be around 9.64% 4.
• The incidence of dyspepsia with tirzepatide has been reported to be around 7.13% 4, while the incidence of constipation has been reported to be around 2.54% 4.

Comparison with Other Treatments

• Tirzepatide has been compared to other treatments, including placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and insulin, in terms of GI symptoms 4, 5, 6.
• Tirzepatide has been found to have a higher incidence of GI symptoms compared to placebo and insulin, but a similar incidence compared to GLP-1 RAs 5, 6.
• The incidence of GI symptoms with tirzepatide has been found to decrease over time, suggesting that long-term treatment may be associated with a lower incidence of GI symptoms 5.

Impact on Weight Reduction

• The impact of GI symptoms on weight reduction with tirzepatide has been evaluated in several studies 6, 7.
• The results suggest that the incidence of GI symptoms, including nausea, vomiting, and diarrhea, does not significantly affect the weight-reducing efficacy of tirzepatide 7.
• Mediation analyses have suggested that the contribution of GI symptoms to the overall difference in weight change between tirzepatide and comparators is minimal (<6%) 7.