Zepbound Becomes First FDA-Approved Drug for Sleep Apnea

For the first time in medical history, a prescription drug has been approved specifically to treat obstructive sleep apnea. Until December 2024, the only FDA-sanctioned treatments were mechanical devices like CPAP machines, oral appliances, and surgery. That changed when the FDA approved Eli Lilly's tirzepatide (brand name Zepbound) for moderate-to-severe OSA in adults with obesity.

The Scale of the Problem

Obstructive sleep apnea affects an estimated 83.7 million adults in the United States—roughly 32% of adults aged 20 and older. The condition occurs when throat muscles relax during sleep, blocking the airway and causing repeated breathing interruptions throughout the night.

The clinical consequences are significant: OSA is independently associated with hypertension, type 2 diabetes, stroke, heart failure, atrial fibrillation, and cognitive impairment. Despite this, an estimated 80% of cases remain undiagnosed.

What SURMOUNT-OSA Actually Tested

The FDA approval was based on the SURMOUNT-OSA trial (ClinicalTrials.gov: NCT05412004), a phase 3, randomized, double-blind, placebo-controlled study published in the New England Journal of Medicine in June 2024. The trial was designed with two parallel studies:

Parameter	Study 1 (No PAP)	Study 2 (On PAP)
Population	Unable/unwilling to use CPAP	Already on stable CPAP therapy
Participants	234	235
Baseline AHI	51.5 events/hour	49.5 events/hour
Baseline BMI	39.1 kg/m²	38.7 kg/m²
Treatment	Tirzepatide 10-15mg vs. placebo, weekly injection, 52 weeks

The Primary Endpoint: AHI Reduction

The apnea-hypopnea index (AHI) measures how many times per hour a person stops breathing (apnea) or breathes shallowly (hypopnea) during sleep. Normal is fewer than 5 events per hour. Moderate OSA is 15-30 events/hour; severe is 30+ events/hour.

Both SURMOUNT-OSA studies hit their primary endpoints with highly significant results:

Outcome	Tirzepatide	Placebo	Difference
Study 1: AHI change	−25.3 events/hr	−5.3 events/hr	−20.0 (p<0.001)
Study 2: AHI change	−29.3 events/hr	−5.5 events/hr	−23.8 (p<0.001)
Weight loss (Study 1)	−17.7%	−1.6%	−16.1%
Weight loss (Study 2)	−19.0%	−1.7%	−17.3%

In relative terms, tirzepatide produced a 48-56% reduction in apnea events—approximately 30 fewer breathing disruptions per hour of sleep compared to placebo.

Disease Resolution: What "Remission" Looked Like

Beyond raw AHI reduction, the trial measured how many patients achieved what researchers defined as "disease resolution"—either an AHI below 5 events/hour, or an AHI of 5-14 with an Epworth Sleepiness Scale (ESS) score of 10 or less (indicating no significant daytime sleepiness).

These thresholds matter clinically because they represent the severity levels at which many guidelines suggest CPAP may not be necessary. For roughly half of participants in Study 2, tirzepatide reduced their OSA to a level where mechanical therapy might no longer be recommended.

Secondary Outcomes: Beyond Sleep

The SURMOUNT-OSA investigators tracked several cardiovascular and inflammatory markers that are elevated in OSA patients:

Measure	Tirzepatide Effect	Clinical Significance
Hypoxic burden	Significantly reduced	Less oxygen desaturation during sleep
Systolic blood pressure	Reduced vs. placebo	OSA is major driver of hypertension
hs-CRP (inflammation marker)	Reduced vs. placebo	Associated with cardiovascular risk
Sleep-related impairment (PROMIS)	Improved	Patient-reported quality of life
Daytime sleepiness (ESS)	Improved in Study 1	Key symptom affecting daily function

How the FDA Label Reads

The approved indication is specific: Zepbound is indicated for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity, to be used in combination with a reduced-calorie diet and increased physical activity.

The key eligibility criteria mirror the trial population:

• AHI ≥15 events per hour (moderate-to-severe OSA)
• BMI ≥30 kg/m² (obesity)
• Adults only (not studied in pediatric populations)

Side Effects in SURMOUNT-OSA

The safety profile was consistent with tirzepatide's established pattern in obesity trials. The most common adverse events (vs. placebo):

Adverse Event	Study 1 (Tirzepatide)	Study 1 (Placebo)
Diarrhea	26.3%	12.5%
Nausea	25.4%	10.0%
Vomiting	17.5%	4.2%
Constipation	15.1% (Study 2)	4.4% (Study 2)

GI side effects were generally mild to moderate and most common during dose titration. The boxed warning for thyroid C-cell tumors (based on rodent studies) and warnings for pancreatitis, gallbladder disease, and other risks apply to this indication.

The Mechanism: Weight Loss or Something More?

Obesity is the primary modifiable risk factor for OSA. Excess weight—particularly around the neck and upper airway—contributes directly to airway collapse during sleep. The relationship is well-established: a 10% weight loss typically produces a 20-30% reduction in AHI.

SURMOUNT-OSA participants lost 17-19% of body weight on tirzepatide, which likely accounts for most of the AHI improvement. However, researchers note that some effects—like reduced inflammation—may provide benefits beyond what weight loss alone would predict.

What This Doesn't Tell Us

Several questions remain unanswered by SURMOUNT-OSA:

Weight maintenance. The American Academy of Sleep Medicine emphasized that sustained weight loss is required for continued OSA benefit. If a patient stops tirzepatide and regains weight, OSA severity will likely return. Long-term adherence data beyond 52 weeks is not available.

Non-obesity-related OSA. The approval is limited to patients with obesity. Many OSA cases are related to anatomical factors (jaw structure, airway anatomy) rather than weight. Zepbound is not indicated for these patients.

Cardiovascular outcomes. While SURMOUNT-OSA showed improvements in blood pressure and inflammatory markers, it was not powered to detect differences in hard cardiovascular endpoints (heart attacks, strokes, death). Whether treating OSA with tirzepatide reduces these outcomes is unknown.

Comparison to CPAP. The trial did not directly compare tirzepatide to optimally used CPAP therapy. Study 2 added tirzepatide on top of CPAP but didn't test whether tirzepatide alone matches CPAP efficacy.

Access and Coverage

The OSA indication creates a new potential coverage pathway for Zepbound. Some key considerations:

Medicare Part D may cover Zepbound for the OSA indication—potentially the first time Medicare has covered tirzepatide for any indication, since weight loss alone is typically excluded from Part D coverage. Individual plan formularies vary.

Commercial insurers may be more likely to cover Zepbound when prescribed for OSA than for obesity alone, though prior authorization requirements typically include documentation of a recent sleep study confirming moderate-to-severe OSA (AHI ≥15).

List price remains ~$1,000+ per month without insurance. Eli Lilly offers savings programs for eligible commercially insured patients, but these do not apply if insurance doesn't cover the drug or for Medicare beneficiaries.

Timeline