Beyond Glycemic Control: The Expanding Role of GLP-1 Analogues in Type 2 Diabetes and Metabolic Health
DOI:
https://doi.org/10.12775/QS.2024.36.56722Keywords
type 2 diabetes mellitus, GLP-1 receptor agonist, cardiovascular benefits, weight management, non-alcoholic fatty liver disease, tirzepatide, Chronic kidney disease, personalised medicineAbstract
Introduction and Purpose:T2DM is a metabolic condition with significant global health implications, largely driven by aging populations and the obesity epidemic. Glucagon-like peptide-1 receptor agonists have transformed T2DM treatment by offering benefits that extend beyond blood glucose control, including weight reduction, cardiovascular protection, and potential effects on related metabolic conditions. This review aims to explore the mechanisms of GLP-1 RAs, their clinical applications, and their evolving role in addressing T2DM and its associated complications.
Materials and Methods:The review is based on a detailed analysis of peer-reviewed studies from major scientific databases such as PubMed. The selected literature focuses on the mechanisms, clinical benefits, and new developments in GLP-1 RA therapies, including innovations in drug formulations and combination treatments.
Results:GLP-1 RAs enhance glycemic control by stimulating glucose-dependent insulin secretion and suppressing glucagon release, with a low risk of hypoglycemia. They also facilitate significant weight loss by regulating appetite and slowing gastric emptying. Beyond these core effects, GLP-1 RAs reduce cardiovascular risks, slow the progression of chronic kidney disease, and show promise in managing NAFLD and neuroinflammation. Innovations such as dual and triple agonists and oral GLP-1 RA formulations have further expanded their therapeutic scope, improving patient outcomes and adherence.
Conclusion:GLP-1 RAs represent a significant advancement in the management of T2DM and related metabolic disorders. By addressing interconnected issues such as glycemic control, weight management, and cardiovascular risk, these therapies play a central role in modern metabolic medicine. Ongoing research should focus on long-term outcomes, safety, and personalized approaches to maximize their full potential and accessibility.
References
Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653-662. doi:10.1016/S2213-8587(21)00203-5
Ng E, Shaw JE, Wood A, Maple-Brown LJ, Hare MJ. Glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy in type 2 diabetes. Aust J Gen Pract. 2022;51(7):513-518. doi:10.31128/AJGP-07-21-6057
Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2021;46:101102. doi:10.1016/j.molmet.2020.101102
Wilbon SS, Kolonin MG. GLP1 Receptor Agonists-Effects beyond Obesity and Diabetes. Cells. 2023;13(1):65. Published 2023 Dec 28. doi:10.3390/cells13010065
Melson E, Miras AD, Papamargaritis D. Future therapies for obesity. Clin Med (Lond). 2023;23(4):337-346. doi:10.7861/clinmed.2023-0144
Zhao X, Wang M, Wen Z, et al. GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects. Front Endocrinol (Lausanne). 2021;12:721135. Published 2021 Aug 23. doi:10.3389/fendo.2021.721135
Drucker DJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab. 2022;57:101351. doi:10.1016/j.molmet.2021.101351
Cornell S. A review of GLP-1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once-weekly agents. J Clin Pharm Ther. 2020;45 Suppl 1(Suppl 1):17-27. doi:10.1111/jcpt.13230
Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. In: StatPearls. Treasure Island (FL): StatPearls Publishing; February 29, 2024.
McLean BA, Wong CK, Campbell JE, Hodson DJ, Trapp S, Drucker DJ. Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation. Endocr Rev. 2021;42(2):101-132. doi:10.1210/endrev/bnaa032
Taylor SI, Yazdi ZS, Beitelshees AL. Pharmacological treatment of hyperglycemia in type 2 diabetes. J Clin Invest. 2021;131(2):e142243. doi:10.1172/JCI142243
Weinberg Sibony R, Segev O, Dor S, Raz I. Drug Therapies for Diabetes. Int J Mol Sci. 2023;24(24):17147. Published 2023 Dec 5. doi:10.3390/ijms242417147
Ferhatbegović L, Mršić D, Macić-Džanković A. The benefits of GLP1 receptors in cardiovascular diseases. Front Clin Diabetes Healthc. 2023;4:1293926. Published 2023 Dec 8. doi:10.3389/fcdhc.2023.1293926
Myasoedova VA, Bozzi M, Valerio V, et al. Anti-Inflammation and Anti-Oxidation: The Key to Unlocking the Cardiovascular Potential of SGLT2 Inhibitors and GLP1 Receptor Agonists. Antioxidants (Basel). 2023;13(1):16. Published 2023 Dec 20. doi:10.3390/antiox13010016
Holt MK. Mind affects matter: Hindbrain GLP1 neurons link stress, physiology and behaviour. Exp Physiol. 2021;106(9):1853-1862. doi:10.1113/EP089445
Dao K, Shechtman S, Weber-Schoendorfer C, et al. Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services. BMJ Open. 2024;14(4):e083550. Published 2024 Apr 24. doi:10.1136/bmjopen-2023-083550
Zhang T, Perkins MH, Chang H, Han W, de Araujo IE. An inter-organ neural circuit for appetite suppression. Cell. 2022;185(14):2478-2494.e28. doi:10.1016/j.cell.2022.05.007
Karagiannis T, Avgerinos I, Liakos A, et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia. 2022;65(8):1251-1261. doi:10.1007/s00125-022-05715-4
Gorgojo-Martínez JJ, Mezquita-Raya P, Carretero-Gómez J, et al. Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus. J Clin Med. 2022;12(1):145. Published 2022 Dec 24. doi:10.3390/jcm12010145
Nevola R, Epifani R, Imbriani S, et al. GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives. Int J Mol Sci. 2023;24(2):1703. Published 2023 Jan 15. doi:10.3390/ijms24021703
Jastreboff AM, Kushner RF. New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics. Annu Rev Med. 2023;74:125-139. doi:10.1146/annurev-med-043021-014919
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Michał Mazur, Dorota Waz, Jakub Szarłowicz, Zofia Goliszek, Karolina Łucja Sobek, Wiktoria Tabin-Barczak, Aldona Sokołowska, Klaudia Fikas, Kamil Chwaliszewski, Sebastian Samuła
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 27
Number of citations: 0