Therapeutic Spectrum of GLP-1 Receptor Agonist: From Glycemic Control to Metabolic Protection
DOI:
https://doi.org/10.12775/QS.2026.49.68001Keywords
GLP-1 receptor agonists, type 2 diabetes mellitus, obesity, cardiovascular protection, renal protection, weight loss, neuroprotectionAbstract
Introduction. Type 2 diabetes mellitus (T2DM) and obesity are major global health challenges. They are associated with cardiovascular, renal, and metabolic complications. Traditional therapies primarily target glycemic control but do not fully prevent long-term complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as multi-organ protective agents, offering benefits beyond glucose lowering.
Aim of the study. This review provides a comprehensive overview of GLP-1 RAs. It covers their pharmacology, glycemic control, obesity management, cardiovascular and renal protection, safety profile, and emerging therapeutic indications. The objective is to highlight their therapeutic potential and support clinicians in individualized treatment planning.
Materials and methods. This narrative review is based on a structured literature search conducted in PubMed and Google Scholar up to September 2025, using the following terms: GLP-1 receptor agonist, type 2 diabetes, obesity, cardiovascular outcomes, renal outcomes, weight loss, and neuroprotection. Additional relevant articles were identified through manual review of reference lists from key publications.
Conclusion. GLP-1 RAs represent multifaceted therapeutic agents that improve glycemic control, induce significant weight loss and confer cardiovascular and renal protection. They are generally well tolerated, with gastrointestinal effects being the most common adverse events. Individualized therapy and ongoing research into novel agents and combination strategies may further enhance clinical outcomes in patients with T2DM, obesity, and cardiometabolic risk.
References
Drucker DJ. GLP-1 receptor agonists: mechanisms of action and therapeutic applications. Cell Metab. 2018;27(6):740–756. doi:10.1016/j.cmet.2018.03.001.
Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17(6):819–837. doi:10.1016/j.cmet.2013.04.008.
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. doi:10.1056/NEJMoa1901118.
Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019;394(10192):39–50. doi:10.1016/S0140-6736(19)31271-1.
Meier JJ. GLP-1 receptor agonists for individualized therapy of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8(12):501–515. doi:10.1038/nrendo.2012.140.
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–2157. doi:10.1053/j.gastro.2007.03.054.
Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, open-label, phase 3, non-inferiority trial (LEAD-6). Lancet. 2009;374(9683):39–47. doi:10.1016/S0140-6736(09)60459-0.
Watanabe Y, Saisho Y, Inaishi J, et al. Efficacy and safety of once-weekly exenatide after switching from twice-daily exenatide in patients with type 2 diabetes. J Diabetes Investig. 2020;11(2):382–388. doi:10.1111/jdi.13146
Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–322. doi:10.1056/NEJMoa1603827.
Marso SP, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–1844. doi:10.1056/NEJMoa1607141.
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. 2019 Jul 13;394(10193):121–130. doi:10.1016/S0140-6736(19)31149-3.
Hernandez AF, et al. Albiglutide and cardiovascular outcomes in type 2 diabetes (HARMONY Outcomes). N Engl J Med. 2018;379(16):1519–1529. doi:10.1016/S0140-6736(18)32261-X
Holman RR, et al. Effects of once-weekly exenatide on cardiovascular outcomes (EXSCEL). N Engl J Med. 2017;377(13):1228–1239. doi:10.1056/NEJMoa1612917.
Husain M, et al. Oral semaglutide and cardiovascular outcomes (PIONEER-6). N Engl J Med. 2019;381(9):841–851. doi:10.1056/NEJMoa1901118.
Kang YM, Jung CH. Cardiovascular effects of glucagon-like peptide-1 receptor agonists. Endocrinol Metab (Seoul). 2016;31(2):258–274. doi:10.3803/EnM.2016.31.2.258.
Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(10):776–785. doi:10.1016/S2213-8587(19)30249-3.
Perkovic V, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(1):109–121. doi:10.1056/NEJMoa2403347
Muskiet MHA, et al. GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nat Rev Nephrol. 2017;13(11):605–628. doi:10.1038/nrneph.2017.123
Smith I, Hardy E, Mitchell S, Batson S. Semaglutide 2.4 mg for the management of overweight and obesity: systematic literature review and meta-analysis. Obes Rev. 2022;23(11):e13401. doi:10.2147/DMSO.S392952
Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373(1):11–22. doi:10.1056/NEJMoa1411892.
Armstrong MJ, et al. Liraglutide safety and efficacy in NASH: LEAN study. Lancet. 2016;387(10019):679–690. doi:10.1016/S0140-6736(15)00803-X.
Hölscher C. Glucagon-like peptide-1 class drugs show clear protective effects in Parkinson’s and Alzheimer’s disease clinical trials: a revolution in the making? Neuropharmacology. 2024;253:109952. doi:10.1016/j.neuropharm.2024.109952
Alharbi SH. Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications. Ther Adv Endocrinol Metab. 2024;15:20420188231153563. doi:10.1177/20420188231222367
Ghosal S, Datta D, Sinha B. A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D). Sci Rep. 2021;11(1):22063. doi:0.1038/s41598-021-01663-y
Wen J, et al. Evaluating the rates of pancreatitis and pancreatic cancer among GLP-1 receptor agonists: a systematic review and meta-analysis of randomised controlled trials. Endocrinol Diabetes Metab. 2025;8(1):e70113. doi:10.1002/edm2.70113.
Liu Y, Tian Q, Yang J, Wang H, Hong T. No pancreatic safety concern following glucagon-like peptide-1 receptor agonist therapies: a pooled analysis of cardiovascular outcome trials. Diabetes Metab Res Rev. 2018 Nov;34(8):e3061. doi: 10.1002/dmrr.3061.
Brito JP, Herrin J, Swarna KS, et al. GLP-1RA Use and Thyroid Cancer Risk. JAMA Otolaryngol Head Neck Surg. 2025 Mar 1;151(3):243–252. doi:10.1001/jamaoto.2024.4852.
Baxter SM, Lund LC, Andersen JH, Brix TH, Hegedüs L, Hsieh MHC, et al. Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study. Thyroid. 2025 Jan;35(1):69–78. doi: 10.1089/thy.2024.0387.
American Diabetes Association. Standards of Medical Care in Diabetes—2025. Diabetes Care. 2025;48(Suppl 1):S1–S106. doi:10.2337/dc25-S001.
KDIGO 2022 Clinical Practice Guideline for Diabetes Management in CKD. Kidney Int. 2022;102(Suppl 4):S1–S127. doi:10.1016/j.kint.2022.06.008
Marx N, Federici M, Schütt K, Müller-Wieland D, et al.; ESC Scientific Document Group. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44:4043–4141. doi:10.1093/eurheartj/ehad192.
Karagiannis T, Malandris K, Avgerinos I, Stamati A, Kakotrichi P, Liakos A, et al. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: systematic review and network meta-analysis of RCTs. BMJ. 2022;377:e067129. doi:10.1007/s00125-024-06144-1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Marta Kamińska, Wiktoria Kotlarz, Matylda Kuczma, Adrianna Klimczak, Barbara Pietrzak, Mikołaj Patelski, Maciej Czapla, Mateusz Surma, Wiktoria Mikusek, Jakub Molenda

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 24
Number of citations: 0