Three days ago Biohack reported Eli Lilly’s claim that its experimental weekly shot, retatrutide, beat Ozempic on weight loss in people with type 2 diabetes (read that article). Those figures came from a company press release. This update is about a different result, and it rests on stronger footing. Two trials testing the same shot in people with obstructive sleep apnea have now been published in The New England Journal of Medicine, a major peer-reviewed medical journal1.
What happened
Obstructive sleep apnea is a common disorder in which breathing stops again and again during sleep. It lowers oxygen levels and causes snoring and daytime sleepiness1. It is often undiagnosed, but current estimates suggest it affects up to one-third of adults in the United States1. Obesity is one of its main risk factors1.
In the two new trials, people who got weekly retatrutide shots had far fewer breathing pauses during sleep after 80 weeks than people who got placebo (dummy) shots2. Up to 50% of participants had only mild sleep apnea by the end of the trials1.
Retatrutide is made by Eli Lilly. It acts on three hormone receptors involved in appetite and metabolism: the GLP-1 receptor targeted by semaglutide (Ozempic, Wegovy), the GIP receptor also targeted by tirzepatide (Mounjaro, Zepbound), and the glucagon receptor21. That is why it is called a “triple” hormone drug.
How the trials worked
There were two trials. TRIUMPH-1-OSA enrolled 243 people without type 2 diabetes, and TRIUMPH-2-OSA enrolled 448 people with type 2 diabetes1. Everyone had overweight or obesity, with a body mass index above 27, and moderate to severe sleep apnea, meaning at least 15 breathing pauses per hour of sleep1.
Both trials were randomized and double-blind: participants were assigned by chance, and neither they nor the researchers knew who got the real drug1. People were split into four groups: placebo, or 4, 9 or 12 milligrams of retatrutide1. The sleep apnea groups were smaller sections built into two larger Lilly trials, TRIUMPH-1 and TRIUMPH-23.
The main measure was the apnea-hypopnea index, a count of how many times per hour breathing stops or becomes very shallow during sleep2.
The results
In people without diabetes, the index fell by 34.3 events per hour on the 9 mg dose and 31.7 on the 12 mg dose, compared with 9.9 on placebo3. In people with diabetes, the drop at those doses was about 25 events per hour, against about 10 on placebo3.
Taking the placebo group’s improvement into account, the 9 mg and 12 mg doses cut roughly 14 to 24 more breathing events per hour than dummy shots, across the two trials2. Weight loss at the highest reported levels was about 22% in one trial and 19% in the other2.
These published numbers are smaller than the ones Lilly put out in June. Its press release then said retatrutide reduced the index by up to 36.1 events per hour, or 60.6%, from a starting average of 58.64. Part of the gap comes from how results are counted. Lilly’s releases lead with an estimate of what the drug does if everyone keeps taking it, while journal papers usually count everyone who started the trial, including people who stopped the drug early3.
Ron Grunstein, the paper’s lead author and a professor of sleep medicine at the Woolcock Institute of Medical Research in Australia, told Medical News Today:
“I think the finding is very important because there are many people with moderate to severe sleep apnea who are looking for alternative treatments to nasal CPAP and, as we emphasised in the paper retatrutide is providing an extra benefit for improving metabolic syndrome or metabolic dysfunction, which CPAP does not provide.”
What it does not show yet
Sleep apnea raises the risk of heart disease, type 2 diabetes and dementia1. But these trials did not show that retatrutide prevents heart attacks, strokes or memory decline2. They measured breathing pauses and weight, not those outcomes.
Fewer breathing pauses also does not necessarily mean the disorder has gone away2. And it is still an open question how much of the improvement comes from weight loss itself and whether the drug has other effects on breathing2.
Mir Ali, a bariatric surgeon at MemorialCare’s Orange Coast Medical Center who was not involved in the research, put it this way:
“Obstructive sleep apnea (OSA) improving with weight loss is a well-established finding in morbidly obese patients, regardless of how the weight loss is achieved.”
Side effects also matter. The sources read for this article did not break them out for the sleep apnea groups. In the larger TRIUMPH-1 trial, Lilly reported that nausea affected 42.4% of people on the 12 mg dose versus 14.8% on placebo, and vomiting 25.3% versus 4.8%3. About 11.3% stopped the 12 mg dose because of side effects, against 4.9% on placebo3. An unusual skin-sensation side effect called dysesthesia was also more common on the drug3.
Who is behind it
Retatrutide is an investigational drug developed by Eli Lilly2, and the sleep apnea groups are part of Lilly’s own late-stage trial program4. Lilly also sells Zepbound (tirzepatide), a competing approach to the same conditions4. The sources read for this article did not detail the funding statement or the authors’ financial ties to the company.
Lilly has promoted the sleep apnea results before. Its June release called the drug’s range of effects “striking,” in the words of Kenneth Custer, president of Lilly Cardiometabolic Health4. The October paper is the first full, peer-reviewed report of these sleep apnea results3.
How it fits the field
The main treatment for sleep apnea today is a CPAP machine, a device that pushes air through a mask over the nose and mouth during sleep1. It works only when people use it consistently5.
Weight-loss drugs have been moving into this space. In 2024, two trials of tirzepatide in 469 people with obesity and moderate to severe sleep apnea, also published in The New England Journal of Medicine, found significant drops in breathing interruptions after 52 weeks5. Tirzepatide is now FDA-approved for moderate to severe obstructive sleep apnea in adults with obesity2. The retatrutide trials ran longer, at 80 weeks, and included a separate trial for people with type 2 diabetes21. The two drugs have not been compared directly for sleep apnea in the sources read here.
Not everyone with sleep apnea has obesity, and weight loss alone does not address every cause of a collapsing airway, such as the shape of the face and jaw or how the airway muscles respond2.
What to watch next
Retatrutide is still in late-stage testing and is not licensed by the FDA or any other regulator1. Lilly has now published several of its large trials, including the main obesity trial and the diabetes trial3. Next steps to follow: whether Lilly files for approval, whether sleep apnea is part of that filing, and whether longer studies show effects on heart health and other outcomes that these trials did not measure.
