Application and Mechanism of GLP-1 Receptor Agonists in the Treatment of Obesity Complicated with Type 2 Diabetes Mellitus

Xingyu Liu; Mao Shu

doi:10.62051/ijphmr.v3n3.08

Authors

Xingyu Liu
Mao Shu

DOI:

https://doi.org/10.62051/ijphmr.v3n3.08

Keywords:

T2DM, GLP-1 RAs, Obesity complicated, GLP-1, HbA1c

Abstract

Obesity and type 2 diabetes mellitus (T2DM) are the main metabolic diseases in the world, and they are closely related in pathogenesis. Obesity can induce insulin resistance and chronic inflammation, while T2DM is often accompanied by abnormal distribution of body fat, which further aggravates metabolic disorder. Traditional treatment methods have some problems, such as hypoglycemia risk, weight gain and limited long-term curative effect. Therefore, the development of new hypoglycemic and weight-reducing drugs has become a clinical demand. GLP-1 receptor agonists (GLP-1 RAs), as a new generation of hypoglycemic drugs, has become a breakthrough in the treatment of obesity complicated with T2DM with its unique glucose-dependent hypoglycemic mechanism, significant weight loss effect and potential cardiovascular protection. By activating GLP-1 receptors, GLP-1 RAs enhance insulin secretion, suppress glucagon release, delay gastric emptying, and inhibit appetite, thereby improving glycemic control and reducing energy intake. Multiple clinical trials have confirmed that GLP-1 RAs can significantly lower glycated hemoglobin (HbA1c) levels, reduce body weight by 5%-15%, and decrease the risk of cardiovascular events by 13%-26%. However, their mechanism of action has not been fully elucidated, and differences in efficacy and long-term safety still require further investigation. This article reviews the current application of GLP-1 RAs in the treatment of obesity combined with T2DM, explores their multi-faceted mechanisms of action in glycemic control, weight loss, and cardiovascular protection, and analyzes their efficacy and safety based on the latest clinical research data to provide a reference for rational clinical use.

References

[1] Nauck, M. A., & D'Alessio, D. A. (2022). Tirzepatide, a dual gip/glp-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Cardiovascular Diabetology, 21(1), 1-16.

[2] Karagiannis, T., Avgerinos, I., Liakos, A., Del Prato, S., Matthews, D. R., & Tsapas, A., et al. (2022). Management of type 2 diabetes with the dual gip/glp-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia, 65(8), 1251-1261.

[3] Shabil, M., Khatib, M. N., Ballal, S., Bansal, P., Tomar, B. S., & Ashraf, A., et al. (2024). Risk of hepatocellular carcinoma with glucagon-like peptide-1 receptor agonist treatment in patients: a systematic review and meta-analysis. BMC Endocrine Disorders, 24(1), 1-11.

[4] Palecek, E. J., Kimzey, M. M., Zhang, J., Marsden, J., Bays, C., & Moran, W. P., et al. (2024). Glucagon-like peptide-1 receptor agonist therapy effects on glycemic control and weight in a primary care clinic population. Journal of Investigative Medicine, 72(8), 911–919.

[5] Zhao, M. B. T., Tifei Xu Tifei XuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai , ChinaMore by Tifei Xu, Xu, T., Xu, M. B. T., &, et al. (2023). Discovery of novel 5, 6-dihydro-1, 2, 4-triazine derivatives as efficacious glucagon-like peptide-1 receptor agonists. Journal of Medicinal Chemistry, 66(12), 7988-8010.

[6] Tuersun, A., Hou, G., & Cheng, G. (2024). Efficacy and safety of the combination or monotherapy with glp-1 receptor agonists and sglt-2 inhibitors in type 2 diabetes mellitus: an update systematic review and meta-analysis. The American Journal of the Medical Sciences, 368(6), 579-588.

[7] Neves, J. S., Borges-Canha, M., & Vasques-Novoa, FranciscoGreen, Jennifer B.Leiter, Lawrence A.Granger, Christopher B.Carvalho, DavideLeite-Moreira, AdelinoHernandez, Adrian F.Del Prato, StefanoMcMurray, John J. V.Md, Joao Pedro Ferreira. (2023). Glp-1 receptor agonist therapy with and without sglt2 inhibitors in patients with type 2 diabetes. Journal of the American College of Cardiology, 82(6), 517-525.

[8] Klein, K. R., Clemmensen, K. K. B., & Lingvay, A. I. (2024). Occurrence of gastrointestinal adverse events upon glp-1 receptor agonist initiation with concomitant metformin use: a post hoc analysis of leader, step 2, sustain-6, and pioneer 6. Diabetes care, 47(2), 280-284.

[9] Jagome, T., Velling, S., Tikva, T. B., Maksimtuk, V., Gaur, N., & Reimets, R., et al. (2025). Gaba and glp-1 receptor agonist combination therapy modifies diabetes and langerhans islet cytoarchitecture in a rat model of wolfram syndrome. Diabetology & Metabolic Syndrome, 17(1), 1-15.

[10] Hintze, S. C., & Terkamp, C. (2022). New therapeutic developments in the treatment of type 2 diabetes mellitus. Deutsche medizinische Wochenschrift (1946), 147(10), 626-636.

[11] Lincoff, A. M., Colhoun, H., Emerson, S., Hovingh, G. K., Kabakci, G., & Kahn, S., et al. (2025). Effect of the glp-1 receptor agonist semaglutide on total cardiovascular events in patients with cardiovascular disease and overweight or obesity but no diabetes in the select trial. Journal of the American College of Cardiology, 85(12), 378-378.

[12] Malin, J., Melo, M. H. S. T. D., John, T. A., Wattanachayakul, P., Lo, K. B., & Amanullah, A. M. (2025). Impact of glucagon-like peptide-1 receptor agonist (glp-1a) use in patients with obesity and heart failure with reduced ejection fraction (hfref): a propensitymatched us population based cohort study. Journal of the American College of Cardiology, 85(12), 1658-1658.

[13] He, L., Wang, J., Ping, F., Yang, N., Huang, J., & Li, Y., et al. (2022). Association of glucagon-like peptide-1 receptor agonist use with risk of gallbladder and biliary diseases: a systematic review and meta-analysis of randomized clinical trials. JAMA internal medicine, 182(5), 513-519.