Eli Lilly obesity pill eases sleep apnea in late-stage trial

Eli Lilly’s obesity pill Foundayo significantly reduced the severity of obstructive sleep apnea in a late-stage trial, paving the way for the drugmaker to seek U.S. approval by the end of the year, CNBC reported.

The trial tested Foundayo in two independent studies. The first included 363 patients who were unable or unwilling to use positive airway pressure therapy, the standard treatment for the condition. The second included 349 patients who were already on PAP therapy and continued it during the trial. Researchers measured the apnea-hypopnea index, which records the number of times per hour a person’s breathing shows a restricted or completely blocked airway.

Patients who took Foundayo without PAP therapy had an average of 21.1 fewer AHI events per hour at 52 weeks, compared with a reduction of 4.8 for the placebo. The pill produced an overall AHI reduction of 43.8% in that group, compared with 6.3% for the placebo. About 31.5% of participants in the Foundayo group met the criteria for remission or improvement to mild sleep apnea. Among patients using both Foundayo and PAP therapy, the pill reduced AHI events by 18.3 per hour versus 5.5 for placebo, an overall reduction of 27.5% compared with 3% for placebo.

The pill also reduced what researchers call the hypoxic burden, a measure of how deeply and for how long oxygen levels fall during sleep. That metric fell by 55.9% in patients not using PAP therapy and 45.8% in those using it. Foundayo helped patients lose roughly 11% of their body weight across both groups at 52 weeks and lowered a marker of inflammation.

Obstructive sleep apnea affects nearly 1 billion adults globally, including 80 million people ages 20 and over in the United States, according to the National Council on Aging. Most have never been diagnosed. The condition causes interrupted breathing during sleep, which can lead to hypertension, heart failure, and stroke, according to the National Council on Aging. Treatment options are limited. PAP machines, which force air through a mask to keep airways open, are effective but cumbersome, and many patients abandon them. Lilly’s injected weight loss drug Zepbound became the first medication to win U.S. approval for sleep apnea in December 2024.

Dr. Thomas Seck, senior vice president of product development for Lilly Cardiometabolic Health, said the company plans to submit the trial results to the FDA by year-end. “Foundayo is already making a difference for people living with obesity, and with plans to submit these results to the FDA by the end of the year, we could have the opportunity to help people living with OSA,” Seck said in a release. Foundayo rolled out in the U.S. in April as an obesity treatment.

The safety profile was consistent with other GLP-1 medications. The most common side effects were gastrointestinal: nausea, diarrhea, constipation, and vomiting, generally mild to moderate. About 12% of patients on Foundayo without PAP therapy discontinued due to side effects, compared with 3.8% on placebo. Among patients using both Foundayo and PAP, 6.8% discontinued the drug versus 0.6% on placebo.

What I think

The 43.8% AHI reduction in the non-PAP group is the number that matters for approval. The FDA wants to see a clinically meaningful reduction in apnea events, and a 44% drop is large enough to clear that bar. The comparison to placebo is even more telling: patients on placebo saw a 6.3% reduction, which is the regression-to-the-mean effect you get from participating in a trial. Foundayo produced seven times that improvement, and nearly a third of patients on the drug saw their sleep apnea resolve or improve to mild. That is a result that changes the standard of care.

The pill format is the competitive advantage. Zepbound, Lilly’s injected GLP-1, was approved for sleep apnea in 2024, but injections are a barrier for many patients. A daily pill is easier to start, easier to continue, and easier to fit into a routine. The discontinuation rates in the trial were 12% for the non-PAP group and 6.8% for the PAP group, which is higher than placebo but lower than the dropout rates typically seen with PAP therapy alone. Patients are more likely to stay on a pill than on a machine, and adherence is the single biggest determinant of whether a sleep apnea treatment works in the real world.

The 11% weight loss is the mechanism. Sleep apnea is caused by airway collapse during sleep, and the airway narrows when tissue around it accumulates fat. GLP-1 drugs reduce that fat, which widens the airway, which reduces apnea events. The same mechanism that makes these drugs effective for obesity makes them effective for sleep apnea, and the trial confirms that the benefit is not incidental. The hypoxic burden reduction of 55.9% is a measure of how much the oxygen deprivation improved, and a 56% improvement in oxygenation during sleep has cardiovascular benefits that extend well beyond the sleep apnea diagnosis.

The market opportunity is large. Eighty million Americans have sleep apnea, and most are undiagnosed. The diagnosed population is already a multibillion-dollar market for PAP machines, and a pill that can replace or supplement those machines will capture share from both the device companies and the injected GLP-1 competitors. Lilly is positioning Foundayo as the first oral GLP-1 approved for sleep apnea, and if the FDA accepts the filing by year-end, the approval could come in late 2027. That would give Lilly a head start over any competing oral GLP-1 for the condition, and it would extend the franchise beyond obesity into a new therapeutic category.

The side effect profile is the risk. A 12% discontinuation rate in the non-PAP group means one in eight patients stopped taking the drug because of gastrointestinal symptoms. That is consistent with the GLP-1 class, but it is not trivial. Patients who stop the drug regain the weight and the sleep apnea returns. The long-term value of Foundayo depends on whether patients can tolerate it for years, and the 52-week trial data is the best evidence we have. The 88% who stayed on the drug are the patients who will benefit. The 12% who stopped are the patients who will need a different option, and for them, the PAP machine is still there.