TIRZEPATIDE AND METABOLIC TREATMENT OF OBSTRUCTIVE SLEEP APNEA IN OBESE PATIENTS - EMERGING THERAPEUTIC PERSPECTIVES
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5603Keywords:
Obstructive Sleep Apnea, Tirzepatide, Obesity, Glucagon-Like Peptide-1 Receptor Agonists, Incretins, PolysomnographyAbstract
Obstructive sleep apnea (OSA) is a highly prevalent and underdiagnosed sleep-related breathing disorder characterized by recurrent upper airway obstruction during sleep, leading to intermittent hypoxia and sleep fragmentation. Its incidence continues to rise in parallel with the global obesity epidemic, which represents the most significant modifiable risk factor for OSA. While continuous positive airway pressure remains the gold standard of symptomatic treatment, long-term adherence is often suboptimal, highlighting the need for alternative, disease-modifying therapeutic strategies.
This paper explores the role of incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists, focusing mainly on tirzepatide, in the management of OSA. Current evidence suggests that these medications contribute to significant weight reduction, improvement in metabolic parameters, and potential attenuation of OSA severity, as reflected by reductions in the apnea–hypopnea index and hypoxic burden.
Beyond weight loss, emerging data indicate that incretin-based therapies may influence key pathophysiological mechanisms of OSA, including systemic inflammation, oxidative stress, and ventilatory control instability. These pleiotropic effects may be particularly relevant in non-obese patients, in whom non-anatomical factors play a predominant role. For these reasons, tirzepatide represents a promising therapeutic approach in the management of OSA.
References
Antonaglia, C., & Passuti, G. (2022). Obstructive sleep apnea syndrome in non-obese patients. Sleep and Breathing, 26(2), 513–518. https://doi.org/10.1007/s11325-021-02412-1
Laratta, C. R., Ayas, N. T., Povitz, M., & Pendharkar, S. R. (2017). Diagnosis and treatment of obstructive sleep apnea in adults. CMAJ, 189(48), E1481–E1488. https://doi.org/10.1503/cmaj.170296
Romero, E., Krakow, B., Haynes, P., & Ulibarri, V. (2010). Nocturia and snoring: Predictive symptoms for obstructive sleep apnea. Sleep and Breathing, 14(4), 337–343. https://doi.org/10.1007/S11325-009-0310-2
Edwards, B. A., Eckert, D. J., & Jordan, A. S. (2017). Obstructive sleep apnoea pathogenesis from mild to severe: Is it all the same? Respirology, 22(1), 33–42. https://doi.org/10.1111/resp.12913
Peppard, P. E., Young, T., Barnet, J. H., Palta, M., Hagen, E. W., & Hla, K. M. (2013). Increased prevalence of sleep-disordered breathing in adults. American Journal of Epidemiology, 177(9), 1006–1014. https://doi.org/10.1093/aje/kws342
Basoglu, O. K., & Tasbakan, M. S. (2018). Gender differences in clinical and polysomnographic features of obstructive sleep apnea. Sleep and Breathing, 22(1), 241–249. https://doi.org/10.1007/s11325-017-1482-9
Young, T., Skatrud, J., & Peppard, P. E. (2004). Risk factors for obstructive sleep apnea in adults. JAMA, 291(16), 2013–2016. https://doi.org/10.1001/jama.291.16.2013
Rotenberg, B. W., Murariu, D., & Pang, K. P. (2016). Trends in CPAP adherence over twenty years of data collection. Journal of Otolaryngology - Head & Neck Surgery, 45, Article 43. https://doi.org/10.1186/S40463-016-0156-0
Liu, Q. K. (2024). Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists. Frontiers in Endocrinology, 15. https://doi.org/10.3389/FENDO.2024.1431292
McNicholas, W. T., & Pevernagie, D. (2022). Obstructive sleep apnea: Transition from pathophysiology to an integrative disease model. Journal of Sleep Research, 31(4), Article e13616. https://doi.org/10.1111/JSR.13616
Sigurdardottir, E. S., Gislason, T., Benediktsdottir, B., Janson, C., Franklin, K. A., Lindberg, E., & Bjornsdottir, E. (2022). Female sex hormones and symptoms of obstructive sleep apnea in European women. PLOS ONE, 17(6). https://doi.org/10.1371/journal.pone.0269569
Spector, A. R., Loriaux, D., Alexandru, D., & Auerbach, S. H. (2016). The influence of the menstrual phases on polysomnography. Cureus, 8(11). https://doi.org/10.7759/cureus.871
Abbasi, A., Gupta, S. S., Sabharwal, N., Meghrajani, V., Sharma, S., Kamholz, S., & Kupfer, Y. (2021). A comprehensive review of obstructive sleep apnea. Sleep Science, 14(2), 142–154. https://doi.org/10.5935/1984-0063.20200056
Bassetti, C. L. A., Welter, L. S., Montes-Martinez, M., et al. (2026). Epidemiology and economic burden of sleep disorders in Europe. European Journal of Neurology, 33(2), Article e70463. https://doi.org/10.1111/ene.70463
Frey, W. C., & Pilcher, J. (2003). Obstructive sleep-related breathing disorders in patients evaluated for bariatric surgery. Obesity Surgery, 13(5), 676–683. https://doi.org/10.1381/096089203322509228
Heinzer, R., Vat, S., Marques-Vidal, P., Marti-Soler, H., Andries, D., Tobback, N., Mooser, V., Preisig, M., Malhotra, A., Waeber, G., Vollenweider, P., Tafti, M., & Haba-Rubio, J. (2015). Prevalence of sleep-disordered breathing in the general population: The HypnoLaus study. The Lancet Respiratory Medicine, 3(4), 310–318. https://doi.org/10.1016/S2213-2600(15)00043-0
Corral, J., Sanchez-Quiroga, M. A., Carmona-Bernal, C., Sanchez-Armengol, A., de la Torre, A. S., Durán-Cantolla, J., Egea, C. J., Salord, N., Monasterio, C., Terán, J., Alonso-Álvarez, M. L., Muñoz-Méndez, J., Arias, E. M., Cabello, M., Montserrat, J. M., & Masa, J. F. (2017). Conventional polysomnography is not necessary for the management of most patients with suspected OSA. American Journal of Respiratory and Critical Care Medicine, 196(9), 1181–1190. https://doi.org/10.1164/rccm.201612-2497OC
Fleetham, J., Ayas, N., Bradley, D., Ferguson, K., Fitzpatrick, M., George, C., Hanly, P., Hill, F., Kimoff, J., Kryger, M., Morrison, D., Ryan, F., Series, F., Tsai, W., & Teschler, H. (2011). Canadian Thoracic Society 2011 guideline update. Canadian Respiratory Journal, 18(1), 25–47. https://doi.org/10.1155/2011/506189
Randerath, W., Verbraecken, J., Andreas, S., et al. (2017). Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep. European Respiratory Journal, 49. https://doi.org/10.1183/13993003.00959-2016
Kapur, V. K., Auckley, D. H., Chowdhuri, S., et al. (2017). Clinical practice guideline for diagnostic testing for adult OSA. Journal of Clinical Sleep Medicine, 13(3), 479–504. https://doi.org/10.5664/jcsm.6506
Li, M., Lin, H., Yang, Q., et al. (2025). Glucagon-like peptide-1 receptor agonists for the treatment of obstructive sleep apnea: A meta-analysis. Sleep, 48(4). https://doi.org/10.1093/sleep/zsae280
Luu, S., Chan, D. E. C. Y., Marshall, N. S., et al. (2025). Pharmacotherapy for obstructive sleep apnea: A critical review of randomized placebo-controlled trials. Sleep Medicine Reviews, 84. https://doi.org/10.1016/j.smrv.2025.102169
Malhotra, A., Grunstein, R. R., Fietze, I., et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity. The New England Journal of Medicine, 391(13), 1193–1205. https://doi.org/10.1056/NEJMoa2404881
European Medicines Agency. (2023). Mounjaro (tirzepatide): Summary of product characteristics. https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro
Wen, J., Nadora, D., Truong, A., et al. (2025). Exploring the effects of tirzepatide on obstructive sleep apnea: A literature review. Cureus, 17(3), Article e80164. https://doi.org/10.7759/cureus.80164
Tian, Y., Tian, R., Juan, H., et al. (2025). GLP-1/GIP dual agonist tirzepatide normalizes diabetic nephropathy via PI3K/AKT mediated suppression of oxidative stress. International Immunopharmacology, 146. https://doi.org/10.1016/j.intimp.2024.113877
Messineo, L., Bakker, J. P., Cronin, J., et al. (2024). Obstructive sleep apnea and obesity: A review of epidemiology, pathophysiology and the effect of weight-loss treatments. Sleep Medicine Reviews, 78, Article 101996. https://doi.org/10.1016/J.SMRV.2024.101996
Schwab, R. J., Pasirstein, M., Pierson, R., et al. (2003). Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric MRI. American Journal of Respiratory and Critical Care Medicine, 168(5), 522–530. https://doi.org/10.1164/rccm.200208-866OC
Dixon, J. B., Schachter, L. M., O’Brien, P. E., et al. (2012). Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: A randomized controlled trial. JAMA, 308(11), 1142–1149. https://doi.org/10.1001/2012.jama.11580
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., et al. (2022). Tirzepatide once weekly for the treatment of obesity. The New England Journal of Medicine, 387(3), 205–216. https://doi.org/10.1056/nejmoa2206038
Peppard, P. E., Young, T., Palta, M., et al. (2000). Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA, 284(23), 3015–3021. https://doi.org/10.1001/jama.284.23.3015
Eckert, D. J., White, D. P., Jordan, A. S., et al. (2013). Defining phenotypic causes of obstructive sleep apnea: Identification of novel therapeutic targets. American Journal of Respiratory and Critical Care Medicine, 188(8), 996–1004. https://doi.org/10.1164/rccm.201303-0448OC
Sands, S. A., Edwards, B. A., Terrill, P. I., et al. (2018). Phenotyping pharyngeal pathophysiology using polysomnography in patients with obstructive sleep apnea. American Journal of Respiratory and Critical Care Medicine, 197(9), 1187–1197. https://doi.org/10.1164/rccm.201707-1435OC
Kim, A. M., Keenan, B. T., Jackson, N., et al. (2014). Tongue fat and its relationship to obstructive sleep apnea. Sleep, 37(10), 1639–1648. https://doi.org/10.5665/sleep.4072
Owens, R. L., Edwards, B. A., Eckert, D. J., et al. (2015). An integrative model of physiological traits can be used to predict obstructive sleep apnea and response to non positive airway pressure therapy. Sleep, 38(6), 961–970. https://doi.org/10.5665/sleep.4744
Bhat, B., & N, A. (2025). Tirzepatide in obstructive sleep apnea: A comprehensive review. Journal of Sleep Medicine & Disorders, 9(1), Article 1144.
Javaheri, S., Barbe, F., Campos-Rodriguez, F., et al. (2017). Sleep apnea: Types, mechanisms, and clinical cardiovascular consequences. Journal of the American College of Cardiology, 69(7), 841–858. https://doi.org/10.1016/j.jacc.2016.11.069
Muxfeldt, E. S., Margallo, V. S., Guimaraes, G. M., & Salles, G. F. (2014). Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. American Journal of Hypertension, 27(8), 1069–1078. https://doi.org/10.1093/ajh/hpu023
Drager, L. F., Polotsky, V. Y., O’Donnell, C. P., et al. (2015). Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea. American Journal of Physiology-Heart and Circulatory Physiology, 309(7), H1101–H1111. https://doi.org/10.1152/ajpheart.00094.2015
Reutrakul, S., & Mokhlesi, B. (2017). Obstructive sleep apnea and diabetes: A state of the art review. Chest, 152(5), 1070–1086. https://doi.org/10.1016/j.chest.2017.05.009
Kent, B. D., Grote, L., Ryan, S., et al. (2014). Diabetes mellitus prevalence and control in sleep-disordered breathing: The European Sleep Apnea Database (ESADA). Chest, 146(4), 982–990. https://doi.org/10.1378/chest.13-2403
Blackman, A., Foster, G. D., Zammit, G., et al. (2016). Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: The SCALE sleep apnea randomized clinical trial. International Journal of Obesity, 40(8), 1310–1319. https://doi.org/10.1038/ijo.2016.52
Wilding, J. P. H., Batterham, R. L., Calanna, S., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. The New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMoa2032183
Aron-Wisnewsky, J., Minville, C., Tordjman, J., et al. (2012). Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. Journal of Hepatology, 56(1), 225–233. https://doi.org/10.1016/j.jhep.2011.04.022
Leng, Y., McEvoy, C. T., Allen, I. E., & Yaffe, K. (2017). Association of sleep-disordered breathing with cognitive function and risk of cognitive impairment: A systematic review and meta-analysis. JAMA Neurology, 74(10), 1237–1245. https://doi.org/10.1001/jamaneurol.2017.2180
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Copyright (c) 2026 Magdalena Dubaj, Bartosz Piech, Sabina Kubicz Mzabi, Alicja Judzińska, Justyna Ignarska, Emilia Trojanowska, Kamila Sobczyńska, Magda Terbosh, Julia Osipowska, Marlena Kwolek
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