Zepbound: Injection for Sleep Apnea Treatment

By Brandon Peters, M.D.

Zepbound (tirzepatide) is a prescription drug used to treat obesity, diabetes, and obstructive sleep apnea. As it induces weight loss, this may improve crowding of the upper airway that may contribute to snoring and sleep apnea. Research suggests that it may be an effective tool in long-term management. Zepbound may have side effects, however, and careful consideration of the risks and benefits may inform its use.

Use of Zepbound

Zepbound is available via prescription only. One of the glucagon-like peptide-1 (GLP-1) receptor agonist medications, Zepbound is self-administered via a weekly injection. The 2.5 mg dose is started once weekly for 4 weeks. If tolerated, it may be increased by 2.5 mg monthly to a maximum dose of 15 mg via weekly injection. Due to the gradual increase, it will take 5 months to reach the maximum dose.

It may reduce excess body weight in adults who are overweight or obese (the latter defined as a body mass index, or BMI, above 30 kg/m2). It is also approved to treat moderate-to-severe obstructive sleep apnea (OSA)—with an apnea-hypopnea index (AHI) >15 events per hour—in adults with obesity. It is meant to be used in combination with a reduced-calorie diet and increased physical activity.

It is the first medication to be approved for the treatment of sleep apnea. The use of Zepbound to treat sleep apnea was approved by the U.S. Food and Drug Administration (FDA) on December 20, 2024. This approval was based on the results of the SURMOUNT-OSA trial, reported in the New England Journal of Medicine in June 2024. This pivotal trial showed that people on Zepbound for 1 year reduced, on average, their weight by 20% and their sleep apnea severity by 50.7%. This means that a lot of study subjects with moderate to severe sleep apnea were able to normalize their breathing, although sleep apnea persisted to a lesser degree in many.

How It Works

More research is needed to fully understand how these medications work. Generally, Zepbound selectively binds to and activates glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. This may help to reduce appetite and caloric intake. As weight loss occurs, fat tissue that is deposited at the base of the tongue and along the upper airway may be reduced and this will gradually increase airflow. It may also reduce pressure on the lungs, increasing lung capacity and allowing more air movement. These changes may resolve snoring and sleep apnea.

Pros

• It may address excessive weight, the most reversible and frequent root cause of sleep apnea in certain people.

• It may reduce the severity of sleep apnea, allowing for other treatment options (i.e., oral appliance, Inspire placement) or the cessation of treatment if the condition resolves.

• It may benefit weight-related medical conditions, including diabetes, hyperlipidemia, hypertension, fatty liver disease, and cardiovascular (i.e., heart attack, heart failure, heart arrhythmia) and cerebrovascular (i.e., stroke, dementia) disease.

Cons

• Weight loss is gradual and benefit may not be derived for months or years into treatment.

• It may reduce sleep apnea severity, but the condition may persist.

• It may not resolve sleep apnea in people who have other anatomy or risk factors contributing to the condition.

• It must be used long-term (lifelong) to maintain the reduced weight. If stopped, the excessive weight may come back.

• It may be expensive and not covered by insurance.

• It may be inaccessible due to demand and production/inventory issues.

Who Should Not Use Zepbound

Zepbound should not be used in people with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). The signs of thyroid tumors include a mass in the neck, difficulty swallowing or breathing, and persistent hoarseness.

Anyone with a prior hypersensitivity reaction, such as anaphylaxis or angioedema, to the medication should also abstain from use.

Due to the delay of gastric emptying, Zepbound may reduce the efficacy of oral hormonal contraceptives for 4 weeks after initiating, or changing the dose of the medication, and barrier contraceptive (i.e., condom) use is recommended during this interval. Weight loss is not recommended during pregnancy. There are no data on its use during breastfeeding.

The medication should not be taken with other tirzepatide-containing products or with any glucagon-like peptide-1 (GLP-1) receptor agonists.

Side Effects

Common

The most common side effects relate to gastrointestinal complaints, and the adverse reactions (listed from most to least common) may include:

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Stomach pain

• Upset stomach

• Injection-site reactions

• Fatigue

• Hypersensitivity

• Belching

• Hair loss

• GERD

• Flatulence (farting)

• Bloating

• Dizziness

• Hypotension (low blood pressure)

Severe

At the highest dose (15 mg), 3.1% of people report severe gastrointestinal issues. Vomiting may contribute to dehydration and volume depletion, potentially triggering acute kidney injury or failure. Gallstones (cholelithiasis or cholecystitis) affected 1.1% of people, compared to 1% of controls. Acute pancreatitis, which may be fatal, has rarely been observed with GLP-1 treatment.

Hypersensitivity to the medication, including anaphylaxis, has been noted in 0.1% of users.

As Zepbound lowers blood glucose levels, this can lead to hypoglycemia, especially when used with other medications to treat diabetes. It may also worsen diabetic retinopathy and caution is advised in this condition.

As it delays gastric emptying, there may be an increased risk of pulmonary aspiration in the context of surgery.

Suicidal thoughts or behaviors have been reported with other weight management products and monitoring for mood changes may be indicated.

When to Check With Your Healthcare Provider

If you are experiencing side effects, especially with the initiation of the medication or an increase in its dose, check in with the prescribing provider. It may be necessary to lower the dose or discontinue the use of Zepbound. Any medication changes should be made in consultation with your medical professional.

Summary

Zepbound may be an effective long-term treatment for moderate to severe obstructive sleep apnea in people with obesity. The side effects are generally tolerable, and the gradual loss of weight may provide other health benefits. Due to the slow effects, people should initiate treatment with continuous positive airway pressure (CPAP) therapy for immediate relief of the condition. The CPAP pressure settings may be gradually reduced and a repeat sleep study may be indicated once weight loss plateaus to evaluate whether the condition has resolved. Insurance coverage may vary, and cost and access issues are common barriers to treatment. If stopped, gradual weight gain is likely to occur. Those who use Zepbound in combination with a reduced-calorie diet, increased physical activity, and ongoing CPAP therapy will derive the greatest benefit from its use.

Can Hypothyroidism Cause Obstructive Sleep Apnea?

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repeated interruptions in breathing during sleep due to the relaxation of the throat muscles. This condition can lead to various health complications if left untreated, including cardiovascular problems, daytime fatigue, and cognitive impairments. While obesity is a well-known risk factor for OSA, other underlying health issues may also contribute to its development. One such condition is hypothyroidism, a disorder in which the thyroid gland does not produce enough thyroid hormones. This article explores the relationship between hypothyroidism and obstructive sleep apnea, including potential mechanisms and implications for treatment.

Understanding Hypothyroidism

Hypothyroidism occurs when the thyroid gland, located in the front of the neck, does not produce sufficient amounts of thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3). These hormones play a crucial role in regulating metabolism, energy production, and various bodily functions. Common causes of hypothyroidism include:

Autoimmune Disorders: Hashimoto's thyroiditis is the most common cause of hypothyroidism, where the immune system attacks the thyroid gland.

Thyroid Surgery: Surgical removal of the thyroid can lead to reduced hormone production.

Radiation Therapy: Treatment for thyroid cancer or other head and neck cancers can damage the thyroid gland.

Iodine Deficiency: Iodine is essential for thyroid hormone production, and a deficiency can lead to hypothyroidism.

Symptoms of hypothyroidism can include fatigue, weight gain, cold intolerance, constipation, dry skin, and depression. However, the relationship between hypothyroidism and obstructive sleep apnea is less well understood. If hypothyroidism is severe, stupor and coma may occur.

The Connection Between Hypothyroidism and Obstructive Sleep Apnea

Research suggests that there is a significant association between hypothyroidism and obstructive sleep apnea. Several studies have indicated that individuals with hypothyroidism are at an increased risk of developing OSA. Here are some potential mechanisms that may explain this relationship:

1. Thyroid Hormones and Muscle Tone: Thyroid hormones play a crucial role in maintaining muscle tone and metabolism throughout the body, including the muscles of the upper airway. Hypothyroidism can lead to muscle weakness and reduced muscle tone, making it more likely for the airway to collapse during sleep. This collapse can result in obstructive apneas, where breathing is interrupted due to obstruction in the upper airway as the tongue blocks the throat.

2. Obesity and Metabolism: Hypothyroidism often leads to weight gain due to a slowed metabolism. Increased weight, particularly when fat tissue is deposited at the base of the tongue, can contribute to airway obstruction during sleep. Fat deposits in the neck can also lead to increased pressure on the airway, exacerbating sleep apnea symptoms. The relationship between obesity and OSA is well established, and since hypothyroidism can lead to weight gain, it serves as an indirect contributor to the development of sleep apnea.

3. Fluid Retention and Edema: Hypothyroidism can cause fluid retention, leading to swelling in various parts of the body, including the throat. This swelling can further narrow the upper airway, increasing the likelihood of obstruction during sleep. Edema in the airway tissues can contribute to increased resistance to airflow, making it more challenging to breathe properly during sleep.

4. Decreased Respiratory Drive: The thyroid hormones also play a role in the regulation of the respiratory drive. In hypothyroid patients, decreased levels of thyroid hormones can lead to a reduced response to changes in oxygen and carbon dioxide levels in the blood. This can impair the body’s ability to initiate breathing during apneic episodes, exacerbating the severity of OSA.

5. Neurological Factors: There is evidence to suggest that hypothyroidism can affect the central nervous system, potentially leading to changes in the regulation of breathing patterns during sleep. This dysregulation may contribute to the development or exacerbation of sleep apnea.

Symptoms Overlap

The symptoms of hypothyroidism and obstructive sleep apnea can overlap, making diagnosis challenging. Both conditions can cause excessive daytime sleepiness, fatigue, and cognitive impairments. Individuals with hypothyroidism may already experience fatigue due to hormonal imbalances, which can mask or mimic symptoms of OSA. As a result, it is crucial for healthcare providers to consider the possibility of sleep apnea when evaluating patients with hypothyroidism.

Diagnosis and Treatment Considerations

If you suspect that you have both hypothyroidism and obstructive sleep apnea, it is essential to consult with a healthcare provider. Diagnosis may involve a combination of clinical evaluations, sleep studies (home sleep apnea testing or in-center polysomnography), and thyroid function tests to measure levels of thyroid hormones (T3 and T4) and thyroid-stimulating hormone (TSH).

1. Managing Hypothyroidism: Treatment of hypothyroidism typically involves hormone replacement therapy with levothyroxine, a synthetic form of thyroid hormone. Effective management of hypothyroidism can lead to improved muscle tone and metabolism, which may, in turn, reduce the severity of obstructive sleep apnea.

2. Addressing Obstructive Sleep Apnea: For individuals diagnosed with both conditions, treating sleep apnea is crucial. Treatment options for OSA may include:

-Continuous positive airway pressure (CPAP): This therapy involves wearing a mask connected to a machine that delivers a continuous flow of air, keeping the airway open during sleep.

-Oral appliances: Dental devices can help reposition the jaw and tongue to keep the airway open.

-Lifestyle changes: Weight loss, positional therapy (sleeping on one's side), and avoiding alcohol or sedatives before bedtime can help alleviate symptoms of OSA.

3. Regular Monitoring: Individuals with hypothyroidism and OSA should have regular follow-up appointments to monitor their conditions. Adjustments in thyroid hormone therapy and continuous assessment of sleep apnea treatment efficacy are essential for optimal health outcomes.

Conclusion

Hypothyroidism and obstructive sleep apnea are interconnected conditions that can significantly impact an individual's quality of life. The presence of hypothyroidism may increase the risk of developing OSA through mechanisms such as reduced muscle tone, weight gain, fluid retention, and altered respiratory drive. Given the overlap in symptoms, it is essential for healthcare providers to consider the possibility of sleep apnea in patients with hypothyroidism.

Effective management of both conditions can lead to improved overall health and quality of life. If you suspect you have symptoms of either condition, consult with a healthcare provider for comprehensive evaluation and appropriate treatment options. By addressing hypothyroidism and sleep apnea together, individuals can achieve better sleep quality and overall health.

This article was created using OpenAI’s ChatGPT on August 2, 2024 and it was personally reviewed and edited by Brandon Peters, M.D. to ensure its accuracy. This use of augmented intelligence in this way allows the creation of health information that can be trusted.