GLP-1s
Lauren Howell, PharmD
On December 20, 2024, FDA approved Zepbound (tirzepatide) for the treatment of obstructive sleep apnea in adults with obesity, to be used in combination with a reduced calorie diet and increased physical activity. This makes Zepbound the first drug treatment option for certain patients with sleep apnea.
Obstructive sleep apnea occurs when the upper airway becomes blocked, which can cause pauses in breathing during sleep. Although it can affect anyone, sleep apnea is more common in people who are overweight or obese. Additionally, it affects men at a higher rate than women with an estimated 34% of men in the United States having sleep apnea compared to 17% of women, according to the American Academy of Family Physicians.
Zepbound, a GLP-1 receptor agonist, works by activating receptors of hormones that are secreted from the intestine. This reduces appetite and food intake, therefore leading to weight loss. By reducing body weight, studies have found that Zepbound can also improve obstructive sleep apnea.
Dosing and adverse effects
The recommended starting dose of Zepbound is 2.5 mg injected subcutaneously once weekly for 4 weeks. The dose should be increased in 2.5 mg increments after at least 4 weeks until the recommended maintenance dose is achieved. For the treatment of obstructive sleep apnea, the recommended maintenance dose is 10 mg or 15 mg injected subcutaneously once weekly.
Zepbound carries a boxed warning for the risk of thyroid C-cell tumors. In rats, tirzepatide causes thyroid C-cell tumors, but the risk in humans is unknown. Additionally, Zepbound is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Patients should be counseled on the potential risks and symptoms of thyroid tumors.
The most common adverse reactions reported in patients using Zepbound are nausea, vomiting, constipation, abdominal pain, dyspepsia, injection site reactions, fatigue, hypersensitivity reactions, eructation, hair loss, and GERD. Acute kidney injury, acute gallbladder disease, and acute pancreatitis can also occur. Concomitant use of Zepbound with insulin or an insulin secretagogue may increase the risk of hypoglycemia.
Patients being treated with Zepbound should be monitored for depression and suicidal thoughts. Discontinue Zepbound if these symptoms occur. Pulmonary aspiration during general anesthesia or deep sedation has been reported in patients receiving GLP-1s and undergoing elective surgeries or procedures.
Because Zepbound delays gastric emptying, it has the potential to impact the absorption of concomitantly administered oral medications. If pregnancy is recognized during treatment, Zepbound should be discontinued as it may cause fetal harm. Patients of reproductive potential using oral contraceptives should be advised to switch to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation.
Clinical trials
Zepbound’s newest indication was approved based on two randomized, double-blind, placebo-controlled studies. The studies included 469 adults without T2D. One study enrolled participants who used positive airway pressure to treat sleep apnea while the other study enrolled patients who were either unable or unwilling to use positive airway pressure.
The participants in both studies were randomized to either receive 10 mg of Zepbound, 15 mg of Zepbound, or placebo once weekly for 52 weeks. The primary endpoint was the measurement of how many times a person stopped breathing or breathed shallowly per hour during sleep, at week 52.
Participants who received Zepbound experienced both a statistically significant and clinically meaningful reduction in events of apnea or hypopnea compared with placebo. The group that received Zepbound also had a greater proportion of individuals who achieved remission or mild obstructive sleep apnea with resolution of symptoms compared with placebo. The Zepbound group saw a significant decrease in body weight at week 52 compared with placebo, too. ■