Tirzepatide: a dual approach to combat obesity and obstructive sleep apnea
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20252496Keywords:
Tirzepatide, Obesity, Obstructive sleep apnea, GLP-1 and GIP agonist, Apnea-hypopnea indexAbstract
Obesity and obstructive sleep apnea (OSA) are strongly connected conditions that significantly affect morbidity and mortality worldwide. Recurrent airway blockage during sleep is a hallmark of OSA, which is frequently made worse by being overweight, especially by fat deposits around the neck that constrict the airway. This syndrome is associated with a higher risk of heart disease, daytime weariness, and fragmented sleep. The potential option for treating obese conditions and its related problems, such as OSA, is tirzepatide, a new bivalent agonist that targets the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. Tirzepatide has been shown in clinical trials to greatly aid in weight loss; over a 72-week period, reports show reductions in body weight of up to 22.4%. Improved metabolic parameters, such as increased insulin sensitivity and decreased inflammatory markers, are correlated with this significant weight loss. According to research, the apnea-hypopnea index (AHI), a crucial indicator of the severity of OSA, might significantly decline with even modest weight loss. Tirzepatide has been proven in studies to significantly lower AHI; one research found that the drug reduced AHI by an average of -29.3 occurrences per hour when compared to a placebo. In addition to increasing insulin secretion, which improves glycemic control, tirzepatide also reduces hunger through pathways in the central nervous system, which makes weight management easier. Tirzepatide's mode of action is especially pertinent to obesity and OSA since it targets weight gain and metabolic dysregulation, two important contributors in the onset and aggravation of sleep apnea. Tirzepatide's novel mechanism, clinical effectiveness in encouraging weight reduction and reducing the severity of OSA, and the close connection between obesity and OSA are all highlighted in this review, indicating that it may be a game-changing treatment for this dual health issue.
Metrics
References
Britannica, The Editors of Encyclopaedia. "Obesity". 2024. Available at: https://www.britannica.com/ science/obesity. Accessed on 16 May 2025.
Tiwari A, Balasundaram P. Public Health Considerations Regarding Obesity. In StatPearls. StatPearls Publishing: Treasure Island, FL, USA. 2024.
El Ghoch M, Fakhoury R. Challenges and New Directions in Obesity Management: Lifestyle Modification Programmes, Pharmacotherapy and Bariatric Surgery. J Popul Ther Clin Pharmacol. 2019;26:1-4. DOI: https://doi.org/10.15586/jptcp.v26i2.599
Abdelaal M, le Roux CW, Docherty NG. Morbidity and mortality associated with obesity. Ann Transl Med. 2017;5:161. DOI: https://doi.org/10.21037/atm.2017.03.107
Silveira EA, Mendonça CR, Delpino FM, Elias Souza GV, Pereira de Souza Rosa L, de Oliveira C, et al. Sedentary behavior, physical inactivity, abdominal obesity and obesity in adults and older adults: A systematic review and meta-analysis. Clin Nutr ESPEN. 2022;50:63-73. DOI: https://doi.org/10.1016/j.clnesp.2022.06.001
Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJ. Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials. J Acad Nutr Diet. 2015;115(9):1447-63. DOI: https://doi.org/10.1016/j.jand.2015.02.031
Burgess E, Hassmén P, Welvaert M, Pumpa KL. Behavioural treatment strategies improve adherence to lifestyle intervention programmes in adults with obesity: a systematic review and meta-analysis. Clin Obes. 2017;105-14. DOI: https://doi.org/10.1111/cob.12180
Sánchez-de-la-Torre M, Campos-Rodriguez F, Barbé F. Obstructive sleep apnoea and cardiovascular disease. Lancet Respir Med. 2013;1(1):61-72. DOI: https://doi.org/10.1016/S2213-2600(12)70051-6
Romero-Corral A, Caples SM, Lopez-Jimenez F, Somers VK. Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest. 2010;137(3):711-9. DOI: https://doi.org/10.1378/chest.09-0360
Mediano O, González Mangado N, Montserrat JM, Alonso-Álvarez ML, Almendros I, Alonso-Fernández A, et al; el Spanish Sleep Network. International Consensus Document on Obstructive Sleep Apnea. Arch Bronconeumol. 2022;58(1):52-68. DOI: https://doi.org/10.1016/j.arbres.2021.03.017
Chen X, Pensuksan WC, Lohsoonthorn V, Lertmaharit S, Gelaye B, et al. Obstructive sleep apnea and multiple anthropometric indices of general obesity and abdominal obesity among young adults. Int J Soc Sci Stud. 2014;2(3):89-99. DOI: https://doi.org/10.11114/ijsss.v2i3.439
Ding Q, Qin L, Wojeck B, Inzucchi SE, Ibrahim A, Bravata DM, et al. Polysomnographic Phenotypes of Obstructive Sleep Apnea and Incident Type 2 Diabetes: Results from the DREAM Study. Ann Am Thorac Soc. 2021;18(12):2067-78. DOI: https://doi.org/10.1513/AnnalsATS.202012-1556OC
Grimaldi D, Beccuti G, Touma C, Van Cauter E, Mokhlesi B. Association of obstructive sleep apnea in rapid eye movement sleep with reduced glycemic control in type 2 diabetes: therapeutic implications. Diabetes Care. 2014;37(2):355‐63. DOI: https://doi.org/10.2337/dc13-0933
Guo J, Dai L, Luo J, Huang R, Xiao Y. Shorter respiratory event duration is related to prevalence of type 2 diabetes. Front Endocrinol (Lausanne). 2023;14:1105781. DOI: https://doi.org/10.3389/fendo.2023.1105781
Li X, Liu X, Meng Q, Wu X, Bing X, Guo N, et al. Circadian clock disruptions link oxidative stress and systemic inflammation to metabolic syndrome in obstructive sleep apnea patients. Front Physiol. 2022;13:932596. DOI: https://doi.org/10.3389/fphys.2022.932596
Alterki A, Abu-Farha M, Al Shawaf E, Al-Mulla F, Abubaker J. Investigating the relationship between obstructive sleep apnoea, inflammation and cardio-metabolic diseases. Int J Mol Sci. 2023;24(7):6807. DOI: https://doi.org/10.3390/ijms24076807
Tamisier R, Pepin JL, Remy J, Baguet JP, Taylor JA, Weiss JW, et al. 14 Nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011;37(1):119‐28. DOI: https://doi.org/10.1183/09031936.00204209
Trinh MD, Plihalova A, Gojda J, Westlake K, Spicka J, Lattova Z, et al. Obstructive sleep apnoea increases lipolysis and deteriorates glucose homeostasis in patients with type 2 diabetes mellitus. Sci Rep. 2021;11(1):3567. DOI: https://doi.org/10.1038/s41598-021-83018-1
Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab. 2018;18:3-14.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-16.
Wilson JM, Lin Y, Luo MJ, Considine G, Cox AL, Bowsman LM, et al. The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: a post hoc analysis. Diabetes Obes Metab. 2022;24:148-53. DOI: https://doi.org/10.1111/dom.14553
Lilly Investors. FDA Approves Lilly's Zepbound™ (tirzepatide) for Chronic Weight Management, a Powerful New Option for the Treatment of Obesity or Overweight with Weight-Related Medical Problems. 2023. Available at: https://investor.lilly. com/news-releases/news-release-details/fda-approves-lillys-zepboundtm-tirzepatide-chronic-weight. Accessed on 18 May 2025.
Frias JP. Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab. 2020;15(6):379-94. DOI: https://doi.org/10.1080/17446651.2020.1830759
Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018;18:3-14. DOI: https://doi.org/10.1016/j.molmet.2018.09.009
Sinha R, Papamargaritis D, Sargeant JA, Davies MJ. Efficacy and safety of tirzepatide in type 2 diabetes and obesity management. J Obes Metab Syndr. 2023;32:25-45. DOI: https://doi.org/10.7570/jomes22067
Min T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021;12(1):143-57. DOI: https://doi.org/10.1007/s13300-020-00981-0
Sallam M, Snygg J, Allam D, Kassem R. Shifting the Scales: Tirzepatide's Breakthrough in Obesity Management. Cureus. 2024;16(5):e60545. DOI: https://doi.org/10.7759/cureus.60545
Beccuti G, Bioletto F, Parasiliti-Caprino M, Benso A, Ghigo E, Cicolin A, et al. Estimating Cardiovascular Benefits of Tirzepatide in Sleep Apnea and Obesity: Insight from the SURMOUNT-OSA Trials. Curr Obesity Rep. 2024;8:1-4. DOI: https://doi.org/10.1007/s13679-024-00592-x
Yeghiazarians Y, Jneid H, Tietjens JR, Redline S, Brown DL, El-Sherif N, et al. Obstructive sleep apnea and cardiovasculardisease: a scientifc statement from the American heart association. Circulation. 2021;144(3):e56-67. DOI: https://doi.org/10.1161/CIR.0000000000000988
Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284(23):3015-21. DOI: https://doi.org/10.1001/jama.284.23.3015
Malhotra A, Heilmann CR, Banerjee KK, Dunn JP, Bunck MC, Bednarik J. Weight reduction and the impact on apnea-hypopneaindex: A systematic meta-analysis. Sleep Med. 2024;121:26-31. DOI: https://doi.org/10.1016/j.sleep.2024.06.014
Bucca C, Brussino L, Maule MM, Baldi I, Guida G, Culla B, et al. Clinical and functional prediction of moderate to severe obstructive sleep apnoea. Clin Respir J. 2011;5(4):219-26. DOI: https://doi.org/10.1111/j.1752-699X.2010.00223.x
Dutta D, Surana V, Singla R, Aggarwal S, Sharma M. Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis. Indian J Endocrinol Metab. 2021;25(6):475-89. DOI: https://doi.org/10.4103/ijem.ijem_423_21
Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, et al. Structural determinants of dual incretin receptor agonism by tirzepatide. Proc Natl Acad Sci U S A. 2022;119(13):e2116506119. DOI: https://doi.org/10.1073/pnas.2116506119
Thomas MK, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K, et al. Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2021;106(2):388-96. DOI: https://doi.org/10.1210/clinem/dgaa863
Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. StatPearls. StatPearls Publishing. Treasure Island (FL). 2023.
Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022;327(6):534-45. DOI: https://doi.org/10.1001/jama.2022.0078
Gao L, Lee BW, Chawla M, Kim J, Huo L, Du L, et al. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial. Nat Med. 2023;29(6):1500-10. DOI: https://doi.org/10.1038/s41591-023-02344-1
Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753-86. DOI: https://doi.org/10.2337/dci22-0034
Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, et al; SURMOUNT-OSA Investigators. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024;391(13):1193-205. DOI: https://doi.org/10.1056/NEJMoa2404881
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-16.
Rochira V, Greco C, Boni S, Costantino F, Dalla Valentina L, Zanni E, et al. The Effect of Tirzepatide on Body Composition in People with Overweight and Obesity: A Systematic Review of Randomized, Controlled Studies. Diseases. 2024;12(9):204. DOI: https://doi.org/10.3390/diseases12090204
Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2024;30(6):1784. DOI: https://doi.org/10.1038/s41591-024-02883-1
Zhao L, Cheng Z, Lu Y, Liu M, Chen H, Zhang M, et al. Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial. JAMA. 2024;332(7):551-60. DOI: https://doi.org/10.1001/jama.2024.9217
Human Energy Requirements. Report of a Joint FAO/WHO/UNU Expert Consultation. 2001. Available at: https://www.fao.org/3/y5686e/y5686e 00.html. Accessed on 18 April 2025.
Jang MS, Kim HY, Dhong HJ, Chung SK, Hong SD, Cho HJ, et al. Effect of parapharyngeal fat on dynamic obstruction of the upper airway in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2014;190(11):1318-21. DOI: https://doi.org/10.1164/rccm.201408-1498LE
Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophysiology of sleep apnea. Physiol Rev. 2010;90(1):47-112. DOI: https://doi.org/10.1152/physrev.00043.2008
Kim AM, Keenan BT, Jackson N, Chan EL, Staley B, Poptani H, et al. Tongue fat and its relationship to obstructive sleep apnea. Sleep. 2014;37(10):1639-48. DOI: https://doi.org/10.5665/sleep.4072
Malhotra A, Bednarik J, Chakladar S, Dunn JP, Weaver T, Grunstein R, et al. Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial. Contemp Clin Trials. 2024;141:107516. DOI: https://doi.org/10.1016/j.cct.2024.107516
Grunstein RR, Taylor R, Shinde S, Dunn JP, Bednarik J, Stefanski A, et al. Effect of Tirzepatide on Weight Loss in Patients with Obstructive Sleep Apnea and Obesity from SURMOUNT-1. Sleep. 2024;47(1):A264-5. DOI: https://doi.org/10.1093/sleep/zsae067.0620
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. DOI: https://doi.org/10.1056/NEJMoa2032183
Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al; STEP 2 Study Group. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397(10278):971-84. DOI: https://doi.org/10.1016/S0140-6736(21)00213-0
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-16. DOI: https://doi.org/10.1056/NEJMoa2206038
Rodriguez PJ, Cartwright BM, Gratzl S, Brar R, Baker C, Gluckman TJ, et al. Semaglutide vs tirzepatide for weight loss in adults with overweight or obesity. JAMA Int Med. 2024;184(9):1056-64. DOI: https://doi.org/10.1001/jamainternmed.2024.2525
Yabe D, Kawamori D, Seino Y, Oura T, Takeuchi M. Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy). Diabetes Obes Metab. 2023;25(2):398-406. DOI: https://doi.org/10.1111/dom.14882
Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, et al. Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes. Diabetes Care. 2023;46(5):998-1004. DOI: https://doi.org/10.2337/dc22-1710
Downloads
Published
How to Cite
Issue
Section
