Vnitr Lek 2026, 72(6):374-381 | DOI: 10.36290/vnl.2026.070

GLP-1 receptor agonists in obesity treatment: where we are today and what can we expect?

Dita Pichlerová
Interní klinika 2. lékařské fakulty UK a FN Motol a Homolka, Praha

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represent a major breakthrough in the treatment of obesity and type 2 diabetes. Their ability to reduce body weight is well documented, and the outlook for new anti-obesity drugs in the near future is more than positive. Along with a reduction of up to 15-22% of baseline weight with semaglutide and tirzepatide, evidence is growing for a wide range of metabolic, cardiovascular, liver, kidney, and neurobiological effects that are independent of weight loss itself. This review article summarizes current clinical and preclinical knowledge about the pleiotropic effects of GLP-1 RAs, with a focus on the results of key cardiovascular studies (LEADER, SUSTAIN-6, SELECT, FLOW), data on liver steatosis and steatohepatitis (NASH/MASH), kidney protection, inflammation modulation, sleep apnea, cognitive function, and potential anti-cancer effects. These mechanisms will be key for personalized therapeutic strategies for patients with obesity and its comorbidities.

Keywords: GLP-1 receptor agonists, semaglutide, liraglutide, tirzepatide, obesity, cardiovascular effects, pleiotropic effects.

Accepted: September 15, 2026; Published: October 2, 2026  Show citation

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Pichlerová D. GLP-1 receptor agonists in obesity treatment: where we are today and what can we expect? Vnitr Lek. 2026;72(6):374-381. doi: 10.36290/vnl.2026.070.
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    References

    1. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity (Silver Spring). 2020;28(6):1050-1061. Go to original source...
    2. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med [Internet]. 2021;384(11):989-1002. Available from: . Go to original source... Go to PubMed...
    3. Drucker DJ. The Cardiovascular Biology of Glucagon-like Peptide-1. Cell Metab [Internet]. 2016;24(1):15-30. Available from: . Go to original source...
    4. Drucker DJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab [Internet]. 2022;57:101351. Available from: . Go to original source...
    5. Sposito AC, Berwanger O, de Carvalho LSF, et al. GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data. Cardiovasc Diabetol. 2018;17(1):157. Go to original source...
    6. Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3(3):153-165. Go to original source...
    7. Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841-851. Go to original source...
    8. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med [Internet]. 2022;387(3):205-216. Available from: . Go to original source...
    9. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1). Lancet. 2021;398(10295):143-155. Go to original source...
    10. Lundgren JR, Janus C, Jensen SBK, et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med. 2021;384(18):1719-1730. Go to original source...
    11. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022;327(2):138-150. Go to original source... Go to PubMed...
    12. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet [Internet]. 2019;394(10193):121-130. Available from: . Go to original source... Go to PubMed...
    13. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med [Internet]. 2023;389(24):2221-2232. Available from: . Go to original source... Go to PubMed...
    14. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322. Go to original source...
    15. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-1844. Go to original source...
    16. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med [Internet]. 2024;391(2):109-121. Available from: . Go to original source...
    17. Helmstaedter V, Hahne JM, Haase A, et al. GLP-1 receptor agonists in non-alcoholic fatty liver disease: the current evidence. Int J Mol Sci. 2023;24(9):8168. Go to original source... Go to PubMed...
    18. Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679-690. Go to original source... Go to PubMed...
    19. Newsome PN, Buchholtz K, Cusi K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384(12):1113-1124. Go to original source... Go to PubMed...
    20. Lv W, Wang X, Xu Q, et al. Glukagon-like peptide-1 receptorové agonisty (GLP-1 RAs) pro léčbu nealkoholického tukového onemocnění jater (NAFLD): Systematický přehled. Endokrinol Diabetes Metab [Internet]. 2020;3(3):e00163. Available from: . Go to original source... Go to PubMed...
    21. Rochoń J, Kalinowski P, Szymanek-Majchrzak K, Grąt M. Role agonistů receptorů typu střevo-játra a glukagonu podobných peptidů-1 receptorů v léčbě metabolické dysfunkce spojeného tukového onemocnění jater. World J Gastroenterol. 21. června 2024; 30(23):2964-2980. DOI: 10.3748/WJG.v30.i23.2964. PMID: 38946874; PMCID: PMC11212696. Go to original source... Go to PubMed...
    22. Samson SL, Vellanki P, Blonde L, Christofides EA, Galindo RJ, Hirsch IB, Isaacs SD, Izuora KE, Low Wang CC, Twining CL, Umpierrez GE, Valencia WM. Konsenzuální prohlášení Americké asociace klinické endokrinologie: Komplexní algoritmus pro řízení diabetu 2. typu - aktualizace 2023. Endocr Pract. květen 2023; 29(5):305-340. DOI: 10.1016/j.eprac.2023.02.001. Erratum in: Endocr Pract. září 2023; 29(9):746. DOI: 10.1016/j.eprac.2023.06.009. Erratum in: Endocr Pract. prosinec 2023; 29(12):1025. DOI: 10.1016/j.eprac.2023.09.008. PMID: 37150579. Go to original source... Go to PubMed...
    23. Nadkarni GN, Avula S, Annapureddy N, et al. Incidence of kidney disease outcomes among patients prescribed glucagon-like peptide-1 receptor agonists: systematic review and meta-analysis. J Clin Endocrinol Metab. 2023;108(4):e93-e101.
    24. Agonista receptoru GLP-1 jako modulátor vrozené imunity. Přední imunol. 8. prosince 2022 13:997578. DOI: 10.3389/Fimmu.2022.997578. PMID: 36569936; PMCID: PMC9772276. Go to original source... Go to PubMed...
    25. Yang W, et al. Vliv agonistů GLP-1 receptorů na cirkulující zánětlivé markery u pacientů s diabetem 2. typu: systematický přehled a metaanalýza. Diabetes Obes Metab [Internet]. 2025;27(7):3607-3626. Available from: .
    26. Rizzo M, et al. Agonisté glukagonu podobných peptidů-1 receptorů zlepšují biomarkery zánětu a oxidačního stresu: Systematický přehled a metaanalýza randomizovaných kontrolovaných studií. Diabetes Obes Metab [Internet]. 2021;23(8):1806-1822. Available from: .
    27. Zhang P, Mao C, Sun A, et al. Reálná pozorování agonistů receptorů GLP-1 a inhibitorů SGLT-2 jako možných léčebných metod pro Alzheimerovu chorobu. Alzheimerova porucha. září 2025; 21(9):e70639. DOI: 10.1002/ALZ.70639. PMID: 40898408; PMCID: PMC12404899. Go to original source... Go to PubMed...
    28. Nørgaard CH, Holt A, Zareini B, et al. Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease registries. Alzheimers Dement (N Y) [Internet]. 2022;8(1):e12268. Available from: . Go to original source...
    29. Cummings JL, Atri A, Sano M, et al. Účinnost a bezpečnost perorálního semaglutidu 14 mg (flexibilní dávka) u raného stádia symptomatického Alzheimerovy choroby (evoke a evoke+): dvě studie fáze 3, randomizované, placebem kontrolované. Lancet [Internet]. 2026;407(10544):2167-2179. Available from: . PMID: 41865758. Go to original source...
    30. Blackman A, Foster GD, Zammit G, et al. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes. 2016;40(8):1310-1319. Go to original source... Go to PubMed...
    31. Davies MJ, Aronne LJ, Caterson ID, et al. Liraglutide and cardiovascular outcomes in adults with overweight or obesity: a post hoc analysis from SCALE randomized controlled trials. Diabetes Obes Metab. 2018;20(3):734-739. Go to original source... Go to PubMed...
    32. Wang L, Xu R, Kaelber DC, et al. Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes. JAMA Netw Open [Internet]. 2024;7(7):e2421305. Available from: . Go to original source... Go to PubMed...
    33. Wharton S, Davies M, Dicker D, et al. Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice. Postgrad Med. 2022;134(1):14-19. Go to original source... Go to PubMed...
    34. Wharton S, Astrup A, Carraro R, et al. ; Zkušební skupina STEP UP. Jednou týdně podávat semaglutid 7,2 mg u dospělých s obezitou (STEP UP): randomizovaná, kontrolovaná studie fáze 3b. Lancetní diabetický endokrinol. listopad 2025; 13(11):949-963. DOI: 10.1016/S2213-8587(25)00226-8. Epub 2025 14. září. PMID: 40961952. Go to original source... Go to PubMed...
    35. Knop FK, Aroda VR, do Vale RD, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet [Internet]. 2023;402(10403):705-719. Available from: . Go to original source... Go to PubMed...
    36. Jastreboff AM, Kaplan LM, Frías JP, et al. Orforglipron, a Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med [Internet]. 2025;393(12):1080-1091. Available from: . Go to original source...
    37. Knop FK, Dandona P, Dicker D, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med [Internet]. 2025;393(1):1-14. Available from: .
    38. Jastreboff AM, Kaplan LM, Frías JP, et al.; Výzkumníci studie obezity fáze 2 s Retatrutidem. Trojnásobný agonista hormonů receptorů Retatrutid pro obezitu - studie fáze 2. N Engl J Med. 2023 10. srpna; 389(6):514-526. doi: 10.1056/NEJMoa2301972. Epub 2023 26. června. PMID: 37366315. Go to original source... Go to PubMed...
    39. Kadowaki T, Isendahl J, Khalid U, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med [Internet]. 2025;393(1):15-26. Available from: .

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