Tirzepatide: A New Drug Treatment for Sleep Apnea

Effective treatments for sleep apnea are rare and often uncomfortable, such as the CPAP machines. Enter Tirzepatide, a new drug that may soon become the first FDA-approved drug for treating obstructive sleep apnea (OSA). Developed by Eli Lilly, this drug, originally designed for type 2 diabetes, has shown promising results in clinical trials for reducing apnea events, offering hope for patients seeking alternatives to CPAP.

However, some questions remain unanswered. The long-term efficacy, reliance on weight loss, potential side effects, and the role of Eli Lilly – with a vested financial interest – warrant careful consideration. As we explore the full scope of the drug’s impact, it’s essential to weigh these factors to understand whether Tirzepatide truly represents a lasting solution for all OSA patients.

Key Takeaways

Tirzepatide could become the first FDA-approved drug for treating sleep apnea, providing an alternative to CPAP.
SURMOUNT-OSA Phase 3 trials showed significant reductions in apnea events and weight loss among patients.
The study was funded by Eli Lilly, raising questions about bias in clinical trials.
Side effects include gastrointestinal issues, but long-term safety remains unknown.
DRD-925, another drug currently in trials, could emerge as a more direct treatment of sleep apnea in the future.

Table of Content

Tirzepatide: The Science Behind the First Drug Treatment for Sleep Apnea

What Are Sleep Apnea and Tirzepatide?

Sleep apnea is a common yet serious sleep disorder where breathing repeatedly stops and starts during sleep. The most prevalent form, obstructive sleep apnea (OSA), occurs when the throat muscles relax excessively, leading to blocked airways. OSA is closely linked to obesity because fat deposits around the airway can obstruct normal breathing.

Tirzepatide, originally developed for type 2 diabetes and marketed as Mounjaro and Zepbound, is showing potential as the first drug treatment for OSA. It works by promoting weight loss, a major factor in reducing obstructive sleep apnea symptoms. While its main application was for glycemic control in diabetes, researchers found it has profound effects on obesity, leading to its exploration as a treatment for sleep apnea.

How Does Tirzepatide Work to Treat Sleep Apnea?

Tirzepatide prevents sleep apnea mainly by treating obesity, which is a key driver of obstructive sleep apnea. Tirzepatide is a dual-acting GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. Both of these hormones play critical roles in glucose metabolism, appetite regulation, and fat storage.

Let’s break it down:

1. GLP-1 and GIP Receptor Activation

GLP-1 and GIP are incretin hormones that stimulate insulin secretion in response to food intake, lowering blood sugar levels. However, their roles extend beyond just managing blood sugar:

GLP-1: Primarily slows down gastric emptying and sends signals to the brain to reduce appetite. By suppressing hunger, it helps patients consume fewer calories, leading to weight loss.
GIP: This hormone enhances insulin sensitivity and works synergistically with GLP-1 to regulate fat storage. By activating both receptors, Tirzepatide creates a stronger and more balanced response to control body weight.

2. Appetite Suppression and Weight Loss

Tirzepatide significantly reduces appetite by acting on the brain’s hypothalamus, the region responsible for hunger regulation. When food intake decreases, caloric deficit leads to fat loss, including the fat deposits in the neck and throat that contribute to airway obstruction in obstructive sleep apnea. This reduction in adipose tissue surrounding the airway improves airflow, reducing the number of apnea events.

3. Reduction of Systemic Inflammation

Obesity and sleep apnea are both linked to chronic inflammation. Increased levels of inflammatory markers like hsCRP (high-sensitivity C-reactive protein) are commonly seen in both conditions. Tirzepatide lowers inflammatory markers, which may improve airway muscle function and reduce the occurrence of hypoxic events (low oxygen levels during sleep). By lowering systemic inflammation, the drug helps reduce the severity of hypoxia—the oxygen deprivation caused by obstructed airways during sleep.

4. Improved Cardiovascular Health

Sleep apnea often leads to elevated blood pressure and increases the risk of heart disease. Tirzepatide has been shown to reduce systolic blood pressure by improving vascular function. This is important because sleep apnea contributes to cardiovascular strain through repeated cycles of oxygen deprivation and recovery. By improving vascular health, Tirzepatide helps mitigate the cardiovascular risks associated with sleep apnea and reduces the risk of heart failure outcomes.

5. Glycemic Control and Weight Management Synergy

For people with both type 2 diabetes and sleep apnea, Tirzepatide offers dual benefits by improving blood sugar regulation and reducing body weight. Poor glycemic control is often associated with worsened sleep apnea symptoms due to its impact on inflammation and fat distribution. By simultaneously managing glucose levels and weight, Tirzepatide can provide a comprehensive treatment strategy for these patients.

Key Findings of the Study: Can Tirzepatide Treat Sleep Apnea?

The SURMOUNT-OSA Phase 3 clinical trials of Tirzepatide provide the strongest evidence for its potential approval as the first drug specifically designed to treat obstructive sleep apnea (OSA). These trials, sponsored by Eli Lilly, had an enrollment of 469 participants with moderate-to-severe sleep apnea and obesity. They showed a significant reduction in apnea events, with patients experiencing an average reduction of 25 to 30 apnea-hypopnea events per hour after 52 weeks of treatment compared to 5-6 events in the placebo group.

Detailed Results by Trial

Trial 1 (Non-CPAP Users): In this group, patients who were not using CPAP saw an average reduction of 25.3 apnea events per hour. Those on the placebo only saw a modest reduction of 5.3 events per hour. The estimated treatment difference was a substantial 20 events per hour.
Trial 2 (CPAP Users): For patients already on CPAP therapy, Tirzepatide reduced 29.3 apnea events per hour compared to a 5.5 events/hour reduction in the placebo group. The treatment difference of 23.8 events per hour highlights Tirzepatide’s strong impact, even for patients already undergoing CPAP therapy.

Secondary Outcomes

Beyond reducing the number of apnea events, Tirzepatide also significantly improved several key secondary outcomes:

Body weight: Participants experienced a substantial weight reduction, which is crucial for reducing airway obstruction in obstructive sleep apnea.
Hypoxic burden: The time spent in oxygen-deprived states during sleep was reduced, improving overall oxygen saturation levels.
Inflammation markers: Patients experienced a decrease in high-sensitivity C-reactive protein (hsCRP), indicating reduced systemic inflammation.
Systolic blood pressure: Significant reductions in blood pressure were also observed, which is important since sleep apnea is linked to increased cardiovascular risks.

Importance of the Study for FDA Approval

The findings from these trials are critically important because they form the foundation for Eli Lilly’s push for FDA approval. If approved, Tirzepatide would be the first-ever drug to be approved specifically for the treatment of obstructive sleep apnea, providing patients with an alternative to CPAP machines. The trials’ robust results make a compelling case for its efficacy in reducing sleep apnea severity, and this is a pivotal argument for FDA consideration.

Is Tirzepatide a Good Treatment for Sleep Apnea? A Critical Look.

Eli Lilly’s Financial Motivation: A Driving Force Behind Tirzepatide

One of the key concerns is that the Phase 3 clinical trials of Tirzepatide for patients with sleep apnea were funded by Eli Lilly, the company that stands to profit immensely from the drug’s approval. Eli Lilly has already enjoyed massive success with Tirzepatide for diabetes and weight loss, generating over $5.1 billion in revenue in 2023 alone under the brands Mounjaro and Zepbound. If Tirzepatide is approved for sleep apnea, this revenue could skyrocket.

The global sleep apnea market is enormous. In the U.S. alone, an estimated 80 million people suffer from sleep apnea, with 20 million experiencing moderate-to-severe forms of the condition. Since 70% of OSA patients are obese, a significant portion of them could potentially benefit from Tirzepatide, and Eli Lilly stands to make billions if the drug becomes a first-line treatment for these patients. Considering Tirzepatide is a weekly injection the ongoing nature of this treatment could translate into long-term revenue streams for the company.

While these financial incentives drive innovation in the field, they also raise concerns about bias in the data. It’s essential that independent studies are conducted to verify the results and ensure that the efficacy and safety profiles of the drug hold up over time.

Long-Term Safety and Efficacy: Still Uncertain

Though Tirzepatide has shown impressive results in reducing apnea-hypopnea index (AHI) and inducing weight loss, there are questions about its long-term safety. Obstructive sleep apnea (OSA) is a chronic condition, so patients may need to stay on the drug indefinitely to maintain benefits. Long-term usage of GLP-1 receptor agonists like Tirzepatide can sometimes lead to side effects such as gastrointestinal issues (nausea, vomiting, diarrhea) and, in rare cases, more serious complications like pancreatitis or thyroid tumors. It is unclear whether the drug’s benefits can be sustained over many years without causing adverse health effects.

Moreover, the trials primarily studied 52-week outcomes, so data on long-term efficacy beyond that time period are still missing. Also, pregnant women were not allowed to participate in the trials. Continued research is needed to confirm that the drug remains effective and safe over several years, especially since sleep apnea is a lifetime disorder for many.

Dependency on Weight Loss: A Major Question

One of the most significant mechanisms by which Tirzepatide treats sleep apnea is through weight loss. The drug reduces fat deposits around the neck and airway, which are often responsible for obstructing airflow in obese patients. In the trials, patients lost an average of 18-20% of their body weight, and this reduction played a key role in decreasing their apnea events.

However, this raises a critical question: is Tirzepatide truly addressing the root cause of sleep apnea, or is it simply managing weight? If patients stop taking the drug and regain the weight, there is a high likelihood that their sleep apnea could return. This makes Tirzepatide more of a weight-management tool than a specific OSA treatment, which limits its applicability to non-obese patients and raises concerns about long-term dependency.

Lack of Direct Impact on Airway Muscles

While Tirzepatide addresses obstructive sleep apnea through weight loss and inflammation reduction, it does not directly improve muscle tone in the airways, which is often a crucial factor in sleep apnea. Unlike CPAP machines, which physically keep the airway open, or surgical interventions that adjust the structure of the airway, Tirzepatide’s effects are indirect. This means the drug may be less effective in severe cases where the collapse of the airway is due to muscle weakness or structural anomalies.

Cost and Accessibility: A Potential Barrier

As a biologic drug, Tirzepatide will likely come with a high price tag. For context, Mounjaro, the version of Tirzepatide approved for the treatment of diabetes, already costs around $1,000 per month. Given that sleep apnea patients would need to use the drug weekly for extended periods of time, the cost could be prohibitive for many, especially those without adequate insurance coverage.

While CPAP machines can be cumbersome, they are generally more affordable and covered by insurance. If Tirzepatide proves too expensive, it may not be a viable alternative for most sleep apnea patients, limiting its practical use despite its potential.

The Competition: DRD-925, Another Drug in Development

Tirzepatide is not the only drug treatment being explored for sleep apnea. DRD-925, another drug currently in Phase 3 trials, is also showing promise as a CPAP alternative. Unlike Tirzepatide, DRD-925 works by improving neuromuscular control of the airway. While still further from FDA approval, it represents another potential non-surgical, drug-based treatment for sleep apnea. However, it is unlikely to hit the market before 2026.

When Could Tirzepatide Be Available as a Treatment for Sleep Apnea?

Tirzepatide has received Fast Track designation by the FDA and could be approved as early as 2025 as a treatment for sleep apnea. The findings from the SURMOUNT-OSA Phase 3 trials were presented during a symposium at the American Diabetes Association’s 84th Scientific Sessions on June 21, 2024, and were then submitted to a peer-reviewed journal.

FDA Fast Track Designation

Eli Lilly has received Fast Track designation from the U.S. Food and Drug Administration for its use in treating both moderate-to-severe OSA and obesity. This designation is crucial as it accelerates the review process for drugs that treat serious conditions with unmet medical needs. The Fast Track status allows Eli Lilly to have more frequent communications with the FDA and submit parts of its New Drug Application (NDA) as they become available, instead of waiting for the completion of the entire application.

Planned Submissions to the FDA and Other Agencies

Based on the results from the SURMOUNT-OSA trials, Eli Lilly plans to submit Tirzepatide for approval to the FDA and other global regulatory bodies starting mid-2024. This timeline suggests that if the Fast Track process goes smoothly, FDA approval could occur as early as 2025. Should the FDA grant approval, Tirzepatide would be the first drug specifically approved for treating obstructive sleep apnea, marking a significant advancement in treatment options.

Global Regulatory Submissions

Eli Lilly also plans to submit the drug to regulatory agencies worldwide, which would make Tirzepatide available to a broader range of patients outside the United States. With 80 million Americans suffering from sleep apnea and over 1 billion people globally, the demand for new, effective treatments like Tirzepatide is high.

Conclusion: Is Tirzepatide the Future of Sleep Apnea Treatment?

While the early results of Tirzepatide are encouraging, more independent research is needed to fully understand its potential as a sleep apnea treatment. Eli Lilly’s financial stake in the success of the drug warrants caution, and the long-term safety of the treatment is still unclear. Additionally, other drugs like DRD-925 are being developed, suggesting that drug-based treatments for sleep apnea may soon become a competitive field.

For now, patients with obstructive sleep apnea and obesity may have a new option on the horizon, but it’s important to remain critical and cautious until more data is available.