Lilly's Foundayo pill cut sleep apnea severity in yearlong trials, with an FDA filing next

Eli Lilly's daily obesity pill Foundayo eased obstructive sleep apnea in two yearlong late-stage studies, and the company plans to ask the Food and Drug Administration by the end of the year to approve it for that use. The pill reduced breathing interruptions both in people who don't use a breathing machine and in people who kept using one throughout the trial.

The results were presented Monday at the American Heart Association's Scientific Sessions in Chicago, where the drug was identified by its generic name, orforglipron. Lilly funded the studies. The AHA classifies the findings as preliminary because they have not yet been published in a peer-reviewed journal.

The filing would seek approval for moderate-to-severe obstructive sleep apnea, or OSA, in adults who have obesity or are overweight. Foundayo is already sold in the U.S. for weight loss and became available in April.

Two studies, two kinds of patients

Lilly split the trial into two independent studies built around the most common treatment for sleep apnea: positive airway pressure, or PAP, which delivers air through a mask at night to keep the airway open. CPAP is the most familiar version of these machines.

The first study enrolled 363 adults who couldn't or wouldn't use PAP. The second enrolled 349 people who had been on PAP for at least three months before screening and stayed on it during the trial. In both studies, participants started Foundayo at a low dose and stepped up every four weeks to various maximum doses.

The main measure was the apnea-hypopnea index, or AHI, which counts how many times an hour a sleeper's airway is partly or fully blocked. Doctors use it to grade how severe OSA is and to judge whether treatment is working.

• Without PAP: After 52 weeks, people on Foundayo averaged 21.1 fewer events per hour, compared with 4.8 fewer on placebo. That worked out to a 43.8% drop in AHI, versus 6.3% for placebo. Lilly said 31.5% of those on the pill reached remission or improved to mild OSA.
• With PAP: Foundayo users averaged 18.3 fewer events per hour, versus 5.5 fewer on placebo, a reduction of about 27.5% compared with 3%. Lilly said 19.6% reached remission or mild OSA.

The pill also reduced hypoxic burden, a gauge of how far and for how long oxygen levels fall during sleep, by 55.9% in the group without PAP and 45.8% in the group using it. Across groups, participants lost roughly 11% of their body weight over the year, and a marker of inflammation fell.

Those are solid results, but the remission numbers deserve attention. Roughly two-thirds of patients not using PAP, and about four in five of those using it, still had more than mild sleep apnea after a year on the drug. The pill made the condition meaningfully less severe for many people. For most, it did not make it go away.

Blood pressure and the role of weight loss

The finding most likely to interest cardiologists is blood pressure. Vaishnavi Kundel, the study's presenting author and an associate professor of medicine at the Icahn School of Medicine at Mount Sinai, said pressure dropped about seven points after a year on the drug. She noted that earlier research has found CPAP lowers blood pressure by about two to three points.

"That's a meaningful blood pressure change," Kundel said, adding that untreated moderate-to-severe sleep apnea frequently travels with high blood pressure, which raises the risk of heart disease and stroke.

That comparison sets results from this trial against findings from separate CPAP research, not a head-to-head test, so it is better read as a signal than as proof that the pill outperforms the machine on blood pressure. Still, a seven-point drop in a population at elevated cardiovascular risk is the kind of number that could matter to doctors deciding whom to treat.

The researchers said participants' weight loss likely contributed to the improvements in sleep apnea and in other cardiometabolic measures. They said further studies are needed to explore whether other mechanisms beyond weight loss played a part, for orforglipron or for GLP-1 drugs generally. Participants also reported sleeping better.

The researchers were explicit that the pill is not meant to replace CPAP. They described it as an addition to the available options, one that could be used alongside a machine or by patients who can't or won't use one.

"A convenient daily pill may help expand access to treatment for sleep apnea," Kundel said.

Side effects and dropouts

Lilly said safety and tolerability were generally in line with earlier Foundayo trials. Side effects were mostly gastrointestinal, including nausea, diarrhea, constipation and vomiting, and were generally mild to moderate, a pattern typical of GLP-1 drugs.

Dropouts tell a more pointed story. About 12% of Foundayo users who weren't on PAP stopped taking the drug because of side effects, compared with 3.8% on placebo. Among those using PAP, 6.8% on the pill quit for that reason, versus 0.6% on placebo. For a drug that has to be taken every day for a long time to keep its benefits, tolerability is not a footnote.

Where the pill fits against Zepbound and CPAP

Lilly already owns the first medication approved for sleep apnea in the U.S. Its weekly injection Zepbound, whose active ingredient is tirzepatide, won that approval in December 2024. Outside that drug, patients have had few choices besides PAP machines, which many find cumbersome to wear night after night.

The AHA said the researchers described these as the first large trials of an oral medication for OSA in people with overweight or obesity. That is the real selling point. A pill removes the injection, and for people who have given up on a mask, it offers a treatment they may actually use.

The scale of the condition explains why Lilly is chasing the label. OSA affects nearly 1 billion adults worldwide, including about 80 million Americans ages 20 and older, according to the National Council on Aging. Lilly said most have never been diagnosed. Because untreated sleep apnea is tied to hypertension, heart failure and stroke, a sleep apnea indication also gives Lilly a medical case for the drug that goes beyond weight loss.

From a business standpoint, filing for a second use of a pill that has been on the market only since April looks like a smart move. It widens the pool of patients for whom doctors can justify a prescription on clinical grounds and lets Lilly cover both people who prefer injections and those who don't. The sources don't say what the pill would cost for this use or how insurers would cover it, and that will shape how many of those undiagnosed millions ever try it.

"We could have the opportunity to help people living with OSA," said Dr. Thomas Seck, a Lilly senior vice president of product development. The next concrete step is the FDA submission, which Lilly says is coming before the end of the year.