Zepbound From Eli Lilly and Company

The FDA approved an additional indication for tirzepatide injection (Zepbound; Eli Lilly and Company) for the treatment of moderate to severe obstructive sleep apnea (OSA) in adults with obesity when used with a reduced-calorie diet and increased physical activity. The approval carries the limitation that tirzepatide should not be coadministered with other tirzepatide-containing products or with any glucagon-like peptide-1 (GLP-1) receptor agonist.¹ Although a classic symptom of OSA is snoring, other symptoms include disrupted sleep, excessive daytime sleepiness, and fatigue.²

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PHARMACOLOGY AND PHARMACOKINETICS

Tirzepatide is a glucose-dependent insulinotropic polypeptide receptor and GLP-1 receptor agonist. It reaches maximum plasma concentrations 24 hours after subcutaneous administration and displays an elimination half-life of 5 to 6 days.¹

DOSAGE AND ADMINISTRATION

For the treatment of OSA, the recommended starting dose of tirzepatide is 2.5 mg subcutaneously once weekly for 4 weeks. Because this dose is intended only for initiation and not for maintenance treatment, it should be increased in 2.5-mg increments after at least 4 weeks to a target dose of 10 or 15 mg subcutaneously once weekly.¹

CLINICAL TRIALS

Tirzepatide was evaluated for OSA in SURMOUNT-OSA (NCT05412004), a master protocol clinical trial that included 2 double-blind, placebo-controlled, randomized trials of adults with moderate to severe OSA and obesity. Participants were randomly assigned 1:1 to receive either tirzepatide or placebo. Both trials met the primary end point, which was the change from baseline in the apnea-hypopnea index at week 52.

In study 1, the tirzepatide group experienced 25.³ fewer breathing interruptions per hour compared with 5.3 in the placebo group. In study 2, the tirzepatide group had 29.3 fewer breathing interruptions compared with 5.5 in the placebo group. Additionally, OSA symptoms resolved at week 52 in 42.2% of the tirzepatide group in study 1 and 50.2% in study 2, compared with 15.9% of the placebo group in study 1 and 14.3% of the placebo group in study 2.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Tirzepatide carries a boxed warning stating that the medication causes thyroid C-cell tumors in rats. It is unknown whether it causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. The boxed warning also states that tirzepatide is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2, and that patients should be counseled regarding the potential risk of MTC and symptoms of thyroid tumors. Treatment with tirzepatide is also contraindicated in patients with a known serious hypersensitivity to the medication or any of its components.

The use of tirzepatide has been associated with gastrointestinal adverse reactions and should not be used in patients with severe gastrointestinal disease. Renal function should be monitored in patients who report adverse reactions that could lead to volume depletion. Acute gallbladder disease, acute pancreatitis, and serious hypersensitivity reactions have occurred. Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia, including severe hypoglycemia, and a lower dose of insulin or insulin secretagogue may be necessary. Patients with a history of diabetic retinopathy should be monitored for progression, and patients should be monitored for depression or suicidal thoughts. Pulmonary aspiration during general anesthesia or deep sedation has been reported in patients using GLP-1 receptor agonists who undergo elective surgeries or procedures. Because tirzepatide delays gastric emptying, it may affect the absorption of concomitantly administered oral medications. Tirzepatide may cause fetal harm and should not be used during pregnancy. Women using oral contraceptives should switch to a nonoral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose increase.

The most common adverse reactions are abdominal pain, constipation, diarrhea, dyspepsia, eructation, fatigue, gastroesophageal reflux disease, hair loss, hypersensitivity reactions, injection site reactions, nausea, and vomiting.¹

REFERENCES

1. Zepbound. Prescribing information. Eli Lilly and Company; 2024. Accessed January 24, 2025. https://uspl.lilly.com/zepbound/zepbound.html#pi

2. FDA approves Zepbound (tirzepatide) as the first and only prescription medicine for moderate-to-severe obstructive sleep apnea in adults with obesity. News release. Eli Lilly and Company. December 20, 2024. Accessed January 24, 2025. https://investor.lilly.com/news-releases/news-release-details/fda-approves-zepboundr-tirzepatide-first-and-only-prescription