Lilly says tirzepatide cut sleep apnea events by up to 63% in two phase 3 trials

Eli Lilly said April 17 that tirzepatide reduced the number of times breathing stops or is restricted during sleep by up to about 63% in adults with moderate-to-severe obstructive sleep apnea (OSA) and obesity, and that it plans to seek a new approved use for the drug ^[1]. Tirzepatide is sold as Zepbound in the U.S. and Mounjaro in some markets outside the U.S. ^[1].

The results come from two 52-week phase 3 trials, SURMOUNT-OSA, that together randomized 469 people at sites in the U.S., Australia, Brazil, China, Czechia, Germany, Japan, Mexico and Taiwan ^[1]. One trial enrolled adults who were unable or unwilling to use positive airway pressure (PAP) therapy; the other enrolled adults who were using PAP and planned to keep using it ^[1]. PAP machines keep the airway open during sleep.

In the trial without PAP, tirzepatide at a maximum tolerated dose of 10 mg or 15 mg once weekly lowered the apnea-hypopnea index (AHI) — events per hour of sleep — by a mean of 27.4 events per hour at 52 weeks, compared with 4.8 events per hour for placebo under the efficacy estimand, which counts people who stayed on their assigned treatment ^[1]. In percentage terms that was a 55.0% reduction versus 5.0% for placebo, and average body weight fell 18.1% versus 1.3% ^[1]. Under the treatment-regimen estimand, which includes people who stopped treatment, AHI fell 25.3 events per hour versus 5.3 for placebo ^[1][2].

In the trial where participants continued PAP therapy, AHI fell a mean of 30.4 events per hour versus 6.0 for placebo, a 62.8% reduction versus 6.4%, with body weight down 20.1% versus 2.3% under the efficacy estimand ^[1]. Under the treatment-regimen estimand, the reduction was 29.3 events per hour versus 5.5, or 58.7% ^[1].

Both trials met their primary and key secondary endpoints, Lilly said ^[1]. The widely quoted "up to 63%" figure comes from the trial in which people stayed on PAP, and the numbers shift depending on which estimand is used. Which figure regulators would accept for labeling has not been disclosed.

The overall safety profile in SURMOUNT-OSA was similar to previously reported SURMOUNT and SURPASS trials, Lilly said ^[1]. The most commonly reported side effects were gastrointestinal and generally mild to moderate: diarrhea, nausea and vomiting in the trial without PAP, and diarrhea, nausea and constipation in the trial with PAP ^[1]. The Zepbound label carries warnings about thyroid tumors including thyroid cancer, severe stomach problems, kidney problems, gallbladder problems, pancreatitis, serious allergic reactions, low blood sugar, vision changes in people with type 2 diabetes, and depression or thoughts of suicide; common side effects include nausea, diarrhea, vomiting, constipation and stomach pain ^[1].

Lilly said OSA affects 80 million adults in the U.S., more than 20 million of them with moderate-to-severe disease, and that 85% of cases go undiagnosed ^[1]. "Addressing this unmet need head-on is critical, and while there are pharmaceutical treatments for the excessive sleepiness associated with OSA, tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease," said Jeff Emmick, Lilly's senior vice president of product development ^[1].

Why it matters for patients

There is currently no drug approved to treat obstructive sleep apnea itself; Zepbound is approved for chronic weight management ^[1]. STAT reported that the results pave the way for Zepbound to potentially become the first approved treatment for OSA ^[2]. For patients, that would mean an option aimed at the breathing interruptions rather than only at daytime sleepiness ^[1].

Tirzepatide was tested both alongside and instead of PAP therapy, so the trials do not show it replacing PAP for people who use it successfully — the group that went without PAP was made up of people unable or unwilling to use it ^[1]. Weight loss was substantial in both trials, but how much of the AHI improvement came from weight loss alone was not reported in these topline results. Whether benefits continue past 52 weeks, or what happens when the drug is stopped, has not been reported.

What happens next

The full results are scheduled to be presented at the American Diabetes Association's 84th Scientific Sessions on June 21 at 3:45 p.m. ET and submitted to a peer-reviewed journal ^[1]. Lilly plans to submit to the FDA and other global regulators beginning mid-year, and the FDA has already granted Fast Track designation for moderate-to-severe OSA and obesity ^[1]. A date for an FDA decision has not been disclosed.