Retatrutide, the First Triple Agonist Drug Shown to Cut Sleep Apnea by Up to 50%
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- Uji klinis fase 3 menunjukkan retatrutide menurunkan indeks apnea-hipopnea secara signifikan pada pasien sleep apnea dengan obesitas, baik dengan maupun tanpa diabetes tipe 2.
- Efek terapi tampaknya berasal dari penurunan berat badan, bukan mekanisme langsung pada kontrol pernapasan, sehingga posisinya sebagai alternatif CPAP masih perlu pembuktian independen.
- Dengan prevalensi obesitas yang meningkat, hasil ini membuka jalan bagi pendekatan farmakologis terhadap sleep apnea, meski status regulasi dan harga masih menjadi penentu utama.
Results from two phase 3 clinical trials published in The New England Journal of Medicine position retatrutide as the first therapy candidate to consistently improve symptoms of obstructive sleep apnea (OSA) in patients with obesity, including those with type 2 diabetes. By the end of the 80-week study, nearly half of participants had only mild sleep apnea—a shift that researchers describe as proof of concept that a weight-loss drug can address the root cause, not just the symptoms.
OSA occurs when the upper airway repeatedly narrows or closes during sleep, triggering breathing pauses that lower oxygen saturation and disrupt rest quality. In the United States, the condition is estimated to affect up to a third of the adult population, with most cases undiagnosed. Because obesity is a major risk factor, rising global obesity rates automatically enlarge the OSA burden—and its social costs, from traffic accidents caused by drowsiness to cardiovascular complications and dementia.
Until now, the standard OSA therapy has been continuous positive airway pressure (CPAP), a machine that blows air through a mask to keep the airway open. The device is effective, but patient adherence is often low because it is uncomfortable. Retatrutide offers a different route: a weekly injection that acts on three hormone receptors—GLP-1, GIP, and glucagon—earning it the label of a triple hormone receptor agonist. The drug has not been approved by the FDA or other authorities because it is still in phase 3 testing.
Ron Grunstein, a professor of sleep medicine at the Woolcock Institute of Medical Research in Australia, who led the publication, considers the findings important because many patients with moderate to severe OSA are looking for alternatives to CPAP. He stressed that retatrutide offers an additional benefit in the form of improved metabolic syndrome—something CPAP does not provide. “The weight loss is substantial and patient response is generally positive,” he said, as quoted by Medical News Today.
However, Mir Ali, a bariatric surgeon at the MemorialCare Surgical Weight Loss Center in California, cautioned that improvement in OSA due to weight loss has long been known, regardless of the method. “To be considered an alternative to established therapy, the study must prove that the drug improves OSA independently of weight loss,” he said. Grunstein himself acknowledged there is no evidence that retatrutide acts directly on breathing control; the observed improvement is most likely a consequence of reduced fat mass, especially in the neck and abdominal areas that press on the airway.
What sets retatrutide apart from its predecessors—semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound)—is its ability to activate the glucagon receptor. This combination not only suppresses appetite but also increases energy expenditure and improves the metabolic profile. In the study, many participants with type 2 diabetes shifted to prediabetes, and some even returned to normal blood sugar levels. This effect could expand the drug's market from a mere weight-loss product to a comprehensive therapy for cardiometabolic disease.
For Indonesia, the implications of these findings are relevant given the rising prevalence of obesity and type 2 diabetes, while access to CPAP remains limited due to cost and the availability of sleep services at health facilities. If retatrutide is approved in the future, price will be the main determinant. Grunstein noted that future use will depend heavily on price and availability. On the other hand, regulators such as BPOM need to prepare an evaluation framework for the growing class of hormone agonist drugs, including requirements for local clinical trials and long-term side-effect monitoring.
The remaining question is no longer whether obesity drugs can help sleep apnea, but how large their independent benefit is and who will get access. Follow-up trials that separate the effects of weight loss from other mechanisms will be key. Meanwhile, clinicians around the world are beginning to consider a combination approach: CPAP to keep the airway open during sleep, plus pharmacological therapy to improve metabolism and reduce weight. Whether retatrutide becomes a new standard or a complement, time and long-term data will answer.
