What are the management strategies for Mounjaro (tirzepatide) related delayed gastric emptying, nausea, and diarrhea?

From the Guidelines

To manage Mounjaro (tirzepatide) related delayed gastric emptying, nausea, and diarrhea, start by taking ondansetron (Zofran) 4-8mg as needed 30 minutes before meals, as it has been shown to improve nausea and vomiting in patients with refractory gastroparesis symptoms 1. For nausea management, this approach is supported by the use of 5-Hydroxytryptamine3 (5-HT3) receptor antagonists, which block serotonin receptors in the chemoreceptor trigger zone and inhibit vagal afferents, thereby improving nausea and vomiting. Some key points to consider:

• Eat smaller, more frequent meals and avoid fatty, spicy foods to reduce the burden on the stomach.
• Stay well-hydrated with clear fluids like water, diluted sports drinks, or ginger tea to prevent dehydration.
• For diarrhea, loperamide (Imodium) 2mg after each loose stool (maximum 8mg daily) can help, as it has been shown to reduce diarrhea prevalence and total duration of diarrhea in adults 1.
• Dietary modifications are crucial - follow a bland diet with low-fiber foods like bananas, rice, toast, and avoid caffeine, alcohol, and high-fiber foods during flare-ups.
• If symptoms are severe or persistent despite these measures, contact your healthcare provider as your Mounjaro dose may need adjustment. These side effects typically improve over time as your body adjusts to the medication, usually within 4-8 weeks of starting treatment. The side effects occur because Mounjaro slows stomach emptying and affects gut hormone signaling as part of its mechanism for improving blood sugar control and promoting weight loss. It is essential to note that while these measures can help manage symptoms, they may not completely eliminate them, and ongoing monitoring and adjustment of treatment may be necessary to optimize outcomes.

From the FDA Drug Label

For the Relief of Symptoms Associated with Diabetic Gastroparesis (Diabetic Gastric Stasis) If only the earliest manifestations of diabetic gastric stasis are present, oral administration of metoclopramide may be initiated. However, if severe symptoms are present, therapy should begin with metoclopramide injection (IM or IV) Doses of 10 mg may be administered slowly by the intravenous route over a 1 to 2 minute period. Administration of Metoclopramide Injection, USP up to 10 days may be required before symptoms subside, at which time oral administration of metoclopramide may be instituted.

Managing Mounjaro related delayed gastric emptying nausea and diarrhea may be treated with metoclopramide.

• The recommended dose for diabetic gastroparesis is 10 mg, which may be administered orally or intravenously.
• Severe symptoms may require initial treatment with metoclopramide injection (IM or IV) before switching to oral administration.
• Treatment may be required for up to 10 days before symptoms subside. 2 2

From the Research

Managing Mounjaro Related Delayed Gastric Emptying, Nausea, and Diarrhea

• Mounjaro, also known as tirzepatide, is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) used to treat type 2 diabetes mellitus (T2DM) 3.
• Common side effects of tirzepatide include nausea, vomiting, and diarrhea, which can be dose-dependent 4, 5, 6.
• Delayed gastric emptying associated with GLP1/GIP receptor agonists can increase the risk of developing appendicitis due to changes in gastrointestinal motility 7.
• The incidence rates of nausea, vomiting, constipation, decreased appetite, diarrhea, and dyspepsia are significantly higher in patients receiving tirzepatide compared to comparators 6.
• Tirzepatide has been shown to improve blood pressure and reduce Low-Density Lipoprotein (LDL) cholesterol and triglycerides, but its use is linked to a significant prevalence of gastrointestinal symptoms 3, 6.

Gastrointestinal Adverse Events

• Gastrointestinal (GI) adverse events are the most commonly reported adverse events associated with tirzepatide, and are dose-dependent 4, 5.
• Nausea, diarrhea, and decreased appetite are very common GI adverse events of tirzepatide, and the incidence is positively correlated with dose 5, 6.
• The incidence rates of GI adverse events, including nausea, vomiting, constipation, decreased appetite, diarrhea, and dyspepsia, are significantly higher in patients receiving tirzepatide compared to comparators 6.

Reducing Gastrointestinal Adverse Events

• GI adverse events of tirzepatide decrease gradually over time, so long-term steady medication may be expected to reduce GI adverse events 5.
• More research is required to find ways to reduce the negative effects of tirzepatide and improve therapy for type 2 diabetes patients 6.