General Information

Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist.

Mounjaro is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 

Mounjaro is supplied as an injection for subcutaneous administration. The recommended starting dosage is 2.5 mg injected subcutaneously once weekly After 4 weeks, increase to 5 mg injected subcutaneously once weekly. If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The maximum dosage is 15 mg subcutaneously once weekly. Administer once weekly at any time of day, with or without meals. Inject subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites with each dose.

Mechanism of Action

Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist. It is a 39-amino-acid modified peptide with a C20 fatty diacid moiety that enables albumin binding and prolongs the half-life. Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1. Tirzepatide enhances first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose dependent manner.

Side Effects

Adverse effects associated with the use of Mounjaro may include, but are not limited to, the following:

• nausea
• diarrhea
• decreased appetite
• vomiting
• constipation
• dyspepsia
• abdominal pain

The Mounjaro drug label comes with the following Black Box Warning: Tirzepatide causes thyroid C-cell tumors in rats. It is unknown whether Mounjaro causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined. Mounjaro is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.

Clinical Trial Results

FDA approval was based on results from the phase 3 SURPASS program which included five global registration trials and two regional trials in Japan. These studies ranged from 40 to 52 weeks and evaluated the efficacy and safety of Mounjaro 5 mg, 10 mg and 15 mg as a monotherapy and as an add-on to various standard-of-care medications for type 2 diabetes. The active comparators in the studies were injectable semaglutide 1 mg, insulin glargine and insulin degludec. Participants in the SURPASS program achieved average A1C reductions between 1.8% and 2.1% for Mounjaro 5 mg and between 1.7% and 2.4% for both Mounjaro 10 mg and Mounjaro 15 mg. Although not currently indicated for weight loss, Mounjaro led to significantly greater weight reductions versus comparators, a key secondary endpoint in all SURPASS studies. Participants treated with Mounjaro lost between 12 lb. (5 mg) and 25 lb. (15 mg).