Currently Enrolling Trials
Zepbound (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist.
Zepbound is specifically indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea, or cardiovascular disease).
Zepbound is supplied as an injection for subcutaneous administration.
The recommended starting dosage is 2.5 mg injected subcutaneously once weekly. The 2.5 mg dosage is for treatment initiation and is not intended for chronic weight management.
After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly.
The dosage may be increased in 2.5 mg increments, after at least 4 weeks on the current dose.
The recommended maintenance dosages in adults are 5 mg, 10 mg, or 15 mg injected subcutaneously once weekly.
Consider treatment response and tolerability when selecting the maintenance dosage. If patients do not tolerate a maintenance dosage, consider a lower maintenance dosage.
The maximum dosage of Zepbound is 15 mg injected subcutaneously once weekly.
Recommendations Regarding Missed Dose
- If a dose is missed, instruct patients to administer Zepbound as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
- The day of weekly administration can be changed, if necessary, as long as the time between the two doses is at least 3 days (72 hours).
Mechanism of Action
Tirzepatide is a GIP receptor and GLP-1 receptor agonist. It is an amino acid sequence including 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. GLP-1 is a physiological regulator of appetite and caloric intake. Nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake.
Adverse effects associated with the use of Zepbound may include, but are not limited to, the following:
- abdominal pain
- injection site reactions
- hypersensitivity reactions
- hair loss
- gastroesophageal reflux disease
Coadministration with other tirzepatide-containing products or any GLP-1 receptor agonist is not recommended. The safety and efficacy of coadministration with other products for weight management have not been established.
The Zepbound drug label comes with the following Black Box Warning: In rats, tirzepatide causes thyroid C-cell tumors. It is unknown whether Zepbound 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. Zepbound 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
The FDA approval of Zepbound for chronic weight management (weight reduction and maintenance) in combination with a reduced-calorie diet and increased physical activity was based on two randomized, double-blind, placebo-controlled trials in obese or overweight adults with at least one weight-related condition. These studies measured weight reduction after 72 weeks in a total of 2,519 patients who received either 5 mg, 10 mg or 15 mg of Zepbound once weekly and a total of 958 patients who received once-weekly placebo injections. In both trials, after 72 weeks of treatment, patients who received Zepbound at all three dose levels experienced a statistically significant reduction in body weight compared to those who received placebo, and greater proportions of patients who received Zepbound achieved at least 5% weight reduction compared to placebo.