Tirzepatide Expands Therapeutic Horizon with New Indication for Obstructive Sleep Apnea

Eli Lilly and Company released the latest clinical trial (SURMOUNT-OSA) results of Zepbound, also known as Tirzepatide, in JAMA Netw Open in April, indicatingTirzepatide Injection Significantly Reduced the Apnea-Hypopnea Index in Subjects, which has new applications in treating common sleep disorders, adding to the evidence that the benefits of so-called GLP-1 agonists can extend to a range of conditions.

Obstructive Sleep Apnea(OSA)Characterized by recurrent sleep-state-dependent upper airway collapse, it is a globally recognized major public health issue, affecting up to 936 million adults in the general population. OSA is independently associated with a significantly increased likelihood of hypertension, dyslipidemia, diabetes, life-threatening cardiovascular diseases, and all-cause mortality.Obesity is the main cause of OSA, while long-term clinical research suggests thatThere is a complex interaction between OSA and obesity., The impact of weight loss and lifestyle interventions on OSA and its comorbidities remains uncertain.

This randomized controlled trial enrolled a total of 89 patients with moderate to severe OSA, using the apnea-hypopnea index (AHI, a commonly used indicator for assessing OSA severity), fasting blood levels, and other metrics at 8 weeks and 6 months post-intervention as clinical endpoints.

At the end of the intervention, 23 (57.5%) of the 40 participants in the intervention group improved by one grade, 3 (12.0%) of the 25 participants improved from severe OSA to mild OSA, and 6 (15.0%) of the 40 participants experienced complete resolution of OSA. Six months later,Among the 34 participants in the intervention group, 14 (41.1%) improved by one level, 5 out of 21 participants (23.8%) improved from severe OSA to mild OSA, and 10 out of 34 participants (29.4%) experienced complete resolution of OSA.Notably, in the intervention group, 18 of 40 participants (45.0%) no longer required continuous positive airway pressure (CPAP) therapy (first-line treatment for OSA) at the end of the intervention, and 21 of 34 participants (61.8%) no longer needed CPAP therapy 6 months post-intervention.

This randomized clinical trial indicates that a new 8-week interdisciplinary weight-loss and lifestyle intervention, meticulously designed to align with existing evidence-based clinical practice guidelines, can improve or even alleviate moderate to severe OSA in overweight or obese adults receiving CPAP treatment, along with comorbid conditions.Therefore, this method may be considered a core strategy to address the significant impact of this increasingly common sleep-related breathing disorder.

As early as the preliminary trials of SURMOUNT-OSA, Tirzepatide demonstrated excellent improvement effects in OSA patients. Its efficacy was observed in moderate to severe OSA adult patients with obesity who did not receive PAP treatment.The results showed that after 52 weeks of observation, the average AHI per hour of participants in the Tirzepatide treatment group decreased by 27.4 times compared to before treatment, while the placebo group only decreased by 4.8 times.In addition, key secondary study results showed that the AHI in the Tirzepatide treatment group decreased by 55.0%, compared to only a 5.0% reduction in the placebo group; furthermore, the average body weight of participants in the Tirzepatide treatment group decreased by 18.1% from baseline, while the placebo group only saw a 1.3% reduction. SURMOUNT-OSA Study 2 evaluated the efficacy of Tirzepatide in adults with moderate to severe obstructive sleep apnea and obesity. The results showed that the AHI in the Tirzepatide treatment group decreased by 30.4 events/hour, compared to only a 6.0 events/hour reduction in the placebo group. In key secondary study results, the AHI in the Tirzepatide treatment group decreased by 62.8%, compared to only 6.4% in the placebo group; additionally, the average body weight of participants in the Tirzepatide treatment group decreased by 20.1% from baseline, while the placebo group only saw a 2.3% reduction.

Tirzepatide is currently the only GLP-1R/GIPR drug approved for chronic weight management.In the United States, it is marketed under the brand name Zepbound, while in other global markets, it is known as Mounjaro. The drug has recently successfully completed Phase III clinical trials for OSA, which means that Tirzepatide will further expand its scope of application, not limited to weight loss treatment but extending into new market areas.

As early as November 2023, when the FDA approved Zepbound,The FDA has already made a forward-looking prediction regarding the potential benefits of GLP-1 agonists.Will Not Stop at Blood Sugar and WeightNovo's reported trial results show that Wegovy can prevent heart-related complications. The company recently also released data showing that Ozempic, which contains the same ingredient at different doses, can help treat kidney disease, obesity, and being overweight.

Meanwhile, Tirzepatide, a strong competitor of Wegovy, also shines in fields beyond weight loss and diabetes control.

• Nonalcoholic Steatohepatitis:SURPASS-3 MRI Sub-study Compared Tirzepatide with Degludec Insulin on Liver Fat Content, Visceral Adipose Tissue Volume, and Abdominal Subcutaneous Fat, Showing Over 30% Reduction in Liver Fat Content in Participants Using Tirzepatide Across the Three Study Endpoints.

• Cardiovascular Disease:For cardiovascular disease risk, two Phase 3 trials, SURPASS-CVOT, are currently ongoing for tirzepatide. In China, it is also in the Phase 3 trial stage. The study focuses on patients with type 2 diabetes, atherosclerotic cardiovascular disease, and overweight, and is expected to be completed by October 2024.

• Heart Failure with Preserved Ejection Fraction:Eli Lilly initiated the randomized, double-blind, placebo-controlled Phase 3 study SUMMIT in April 2021 for patients with obesity and heart failure with preserved ejection fraction, enrolling a total of 700 participants, with the study expected to be completed by June 2024.

• Chronic Kidney Disease:Tirzepatide is currently undergoing a Phase 2 clinical trial for patients with chronic kidney disease, known as the TREASURE-CKD study. This study was initiated in February 2023 and is expected to be completed by February 2026, enrolling 149 participants.

On May 13, 2022, Tirzepatide was approved by the FDA for marketing to treat type 2 diabetes. On September 7 of the same year, the marketing application for Tirzepatide injection in China was accepted by the NMPA to improve glycemic control in adult patients with type 2 diabetes.Tirzepatide is also the first new type of diabetes drug in nearly 10 years.。

Notably, on October 3, 2023, Eli Lilly and Company presented the first new China evidence (SURMOUNT-CN) in the field of obesity treatment with Tirzepatide at the 59th Annual Meeting of the European Association for the Study of Diabetes (EASD). Therefore, according to relevant personnel speculation,Expected to launch in China by mid-2024 at the earliest.

Moreover, John Sharretts, head of the FDA's Division of Diabetes, Lipid Disorders, and Obesity, noted in a statement, "Obesity and being overweight are serious conditions that may be associated with some leading causes of death, such as heart disease, stroke, and diabetes," given the rising rates of obesity and overweight in the United States.Therefore, approving emerging multifunctional weight-loss drugs to address unmet medical needs caused by obesity is likely to be the future direction and trend.

Reference:

1.Carneiro-Barrera A, Amaro-Gahete FJ, Guillén-Riquelme A, Jurado-Fasoli L, Sáez-Roca G, Martín-Carrasco C, Buela-Casal G, Ruiz JR. Effect of an Interdisciplinary Weight Loss and Lifestyle Intervention on Obstructive Sleep Apnea Severity: The INTERAPNEA Randomized Clinical Trial. JAMA Netw Open. 2022 Apr 1;5(4):e228212. doi: 10.1001/jamanetworkopen.2022.8212

2.Tirzepatide reduced sleep apnea severity by up to nearly two-thirds in adults with obstructive sleep apnea (OSA) and obesity | Eli Lilly and Company

3.https://scrip.citeline.com/SC150120/Lilly-Can-Rest-Easy-As-Tirzepatide-Scores-Phase-III-Sleep-Apnea-Win