- Two 52-week trials enrolled 469 adults with obesity and moderate-to-severe obstructive sleep apnea, but no diabetes. One group did not use a CPAP-type machine; the other did.1
- Breathing interruptions during sleep (the AHI) fell by about 25 to 29 events per hour on tirzepatide, about half the starting level, vs about 5 per hour on placebo.1
- People on tirzepatide also lost about 18–20% of their body weight. Nausea, diarrhea and other stomach side effects were the most common problems.1
What sleep apnea and AHI mean
In obstructive sleep apnea, the airway in the throat keeps narrowing or closing during sleep. Breathing stops for a moment (an apnea) or becomes very shallow (a hypopnea). Oxygen levels dip, and the brain briefly wakes the body to start breathing again. Most people do not remember these wake-ups, but they can leave you tired during the day. Sleep apnea is also linked to heart and blood vessel problems.1
The apnea–hypopnea index, or AHI, is simply a count. It is the average number of those pauses and shallow-breathing episodes per hour of sleep, measured during an overnight sleep study. In SURMOUNT-OSA, a hypopnea counted when airflow dropped by at least 30% for at least 10 seconds, together with a clear dip in blood oxygen.1
| AHI (events per hour) | What the trial called it |
|---|---|
| Under 15 | Mild (or no) sleep apnea |
| 15 or more | Moderate |
| 30 or more | Severe |
An AHI of 50 means the person's breathing was interrupted about 50 times an hour, close to once a minute. That was roughly the average at the start of these trials.
Who was studied
Adults could join if they had moderate-to-severe obstructive sleep apnea (AHI of 15 or more) and obesity (BMI of 30 or more, or 27 or more in Japan). People with type 1 or type 2 diabetes were excluded.1 There were two separate trials:
- Trial 1 (234 people): not using positive airway pressure (PAP) therapy, such as a CPAP machine, because they could not or would not.
- Trial 2 (235 people): already using PAP for at least three months and planning to keep using it. They paused it for a week before each sleep study so the machine would not mask the results.
About two-thirds or more of participants were men, and the average age was about 48 in trial 1 and 52 in trial 2. Everyone was randomly assigned to weekly tirzepatide or placebo injections. The dose was raised step by step over up to 20 weeks to the highest dose each person tolerated, 10 mg or 15 mg. Both groups also got regular lifestyle counseling: a 500-calorie daily deficit and at least 150 minutes of activity a week.1
What happened to AHI
In events per hour, AHI fell by 25.3 on tirzepatide vs 5.3 on placebo in trial 1, and by 29.3 vs 5.5 in trial 2.1
| After 52 weeks | Trial 1: tirzepatide | Trial 1: placebo | Trial 2: tirzepatide | Trial 2: placebo |
|---|---|---|---|---|
| AHI cut by half or more | 61.2% | 19.0% | 72.4% | 23.3% |
| AHI under 5, or 5–14 without much daytime sleepiness | 42.2% | 15.9% | 50.2% | 14.3% |
| Change in body weight | −17.7% | −1.6% | −19.6% | −2.3% |
| Change in systolic blood pressure* | −9.5 | −1.8 | −7.6 | −3.9 |
The second row matters because, as the authors note, at those levels PAP therapy may not be recommended. Up to half the people on tirzepatide got there. That also means about half or more did not.1
People on tirzepatide also reported less sleep-related impairment and disturbance on questionnaires, and had lower levels of a blood marker of inflammation (hsCRP). The overnight drops in oxygen, measured as "hypoxic burden," improved too.1
Side effects
As in other tirzepatide trials, the most common side effects were stomach-related. They were mostly mild to moderate and happened most often while the dose was being raised.1
| Trial 1: tirzepatide | Trial 1: placebo | Trial 2: tirzepatide | Trial 2: placebo | |
|---|---|---|---|---|
| Diarrhea | 26.3% | 12.5% | 21.8% | 8.8% |
| Nausea | 25.4% | 10.0% | 21.8% | 5.3% |
| Stopped because of side effects | 4.4% | 1.7% | 3.4% | 7.0% |
There were two confirmed cases of acute pancreatitis, both in the trial 2 tirzepatide group, and no deaths in either trial.1 For more on stomach side effects and what tends to help, see our GI side effects article.
What these trials do not tell us
- Long-term effects. Treatment lasted 52 weeks. The trials could not show whether better AHI leads to fewer heart attacks or strokes over time. For a trial that did measure those outcomes with semaglutide, see what SELECT found.
- People without obesity, or with diabetes. Neither group was included.
- Whether to stop using CPAP. Trial 2 was not designed to answer that. Any change to sleep apnea treatment is a decision to make with your sleep doctor.
- What happens after stopping. These trials did not follow people off the medicine. Other trials show that weight tends to come back. See what those found.
The trials were funded by Eli Lilly, which makes tirzepatide.1
Sources
- Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024;391(13):1193-1205. PubMed · Full text (PMC) · doi:10.1056/NEJMoa2404881
