ONE PATHWAY, INFINITE POTENTIAL? THE FUTURE OF GLP-1 THERAPIES: A 2026 CLINICAL UPDATE

Keywords: GLP-1 Receptor Agonists, Semaglutide, Obesity, Alcohol Use Disorder, Metabolic Psychiatry, Gut-Brain Axis

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced from incretin-based therapies for type 2 diabetes to multifaceted treatments addressing obesity, cardiovascular disease, and emerging neuropsychiatric conditions. This review examines their physiological mechanisms, pharmacological profiles, and clinical outcomes based on data through early 2026.

GLP-1 RAs mimic the incretin effect, enhancing insulin secretion, delaying gastric emptying, and modulating central reward pathways in the mesolimbic system. Approved agents like semaglutide and tirzepatide achieve 15-25% weight loss, reduce major adverse cardiovascular events by 12-26%, and show promise in heart failure with preserved ejection fraction and chronic kidney disease.

Recent trials indicate potential in alcohol use disorder, with semaglutide reducing heavy drinking and cravings, though cognitive benefits in major depressive disorder remain unproven. Safety analyses from large cohorts (2024-2025) confirm no increased thyroid cancer risk (HR 0.81-0.93), and FDA reviews (2026) find no causal suicidality link.

Overall, GLP-1 RAs bridge metabolic and behavioral health, supporting a unified view of energy regulation. Ongoing research on patient responders and targeted analogues will guide their integration into care for metabolic psychiatry, emphasizing balanced risk assessment.

References

Arty, F., Shreya, D., Chaudhry, A., & Sarkar, S. (2025). Semaglutide in heart failure with preserved ejection fraction: Emerging evidence and clinical implications. Cureus, 17(7), Article e87605. https://doi.org/10.7759/cureus.87605

Badulescu, S., Gill, H., Shah, H., Brudner, R., Phan, L., Di Vincenzo, J. D., Tabassum, A., Armanyous, M., Llach, C.-D., Rosenblat, J. D., McIntyre, R. S., & Mansur, R. B. (2026). Semaglutide for the treatment of cognitive dysfunction in major depressive disorder: A randomized clinical trial. Med, 7(1), 100916. https://doi.org/10.1016/j.medj.2025.100916 (Original work published 2025)

Baxter, S. M., Lund, L. C., Andersen, J. H., Brix, T. H., Hegedüs, L., Hsieh, M. H.-C., Su, C. T.-T., Cheng, M. C.-Y., Chang, Z. C.-J., Lai, E. C.-C., Hussain, S., Chu, C., Gomes, T., Antoniou, T., Eskander, A., Bouck, Z., Tadrous, M., Bea, S., Choi, E.-Y., Shin, J.-Y., Modig, K., Talbäck, M., Ljung, R., Gulseth, H. L., Karlstad, Ø., Hicks, B., & Pottegård, A. (2025). Glucagon-like peptide 1 receptor agonists and risk of thyroid cancer: An international multisite cohort study. Thyroid, 35(1), 69–78. https://doi.org/10.1089/thy.2024.0387

Drucker, D. J. (2026). The expanding landscape of GLP-1 medicines. Nature Medicine, 32(1), 47–57. https://doi.org/10.1038/s41591-025-04124-5

Guillen, R., Sa, B., Maristany, A., Subramaniam, A., Buonocore, B., Smith, A., Oldak, S. E., & Padilla, V. (2026). Psychiatric effects of GLP-1 receptor agonists: A systematic review of emerging evidence. Diabetes, Obesity and Metabolism, 28(1), 50–59. https://doi.org/10.1111/dom.70198 (Original work published 2025)

Hendershot, C. S., Bremmer, M. P., Paladino, M. B., Kostantinis, G., Gilmore, T. A., Sullivan, N. R., Tow, A. C., Dermody, S. S., Prince, M. A., Jordan, R., McKee, S. A., Fletcher, P. J., Claus, E. D., & Klein, K. R. (2025). Once-weekly semaglutide in adults with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 82(4), 395–405. https://doi.org/10.1001/jamapsychiatry.2024.4789

Indiana University. (2025, October 15). Fairbanks, Lilly and Indiana employers collaborate to study obesity medications’ impact. IU News. https://news.iu.edu/live/news/47651-fairbanks-lilly-and-indiana-employers-collaborate

Kosiborod, M. N., Abildstrøm, S. Z., Borlaug, B. A., Butler, J., Rasmussen, S., Davies, M., Hovingh, G. K., Kitzman, D. W., Lindegaard, M. L., Møller, D. V., Shah, S. J., Treppendahl, M. B., Verma, S., Abhayaratna, W., Ahmed, F. Z., Chopra, V., Ezekowitz, J., Fu, M., Ito, H., Lelonek, M., Melenovsky, V., Merkely, B., Núñez, J., Perna, E., Schou, M., Senni, M., Sharma, K., Van der Meer, P., von Lewinski, D., Wolf, D., & Petrie, M. C. (2023). Semaglutide in patients with heart failure with preserved ejection fraction and obesity. The New England Journal of Medicine, 389(12), 1069–1084. https://doi.org/10.1056/NEJMoa2306963

Pasternak, B., Wintzell, V., Hviid, A., Eliasson, B., Gudbjörnsdottir, S., Jonasson, C., Hveem, K., Svanström, H., Melbye, M., & Ueda, P. (2024). Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ, 385, Article e078225. https://doi.org/10.1136/bmj-2023-078225

U.S. Food and Drug Administration. (2026, January 13). FDA requests removal of suicidal behavior and ideation warning from glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-suicidal-behavior-and-ideation-warning-glucagon-peptide-1-receptor-agonist-glp

Published
2026-02-05
Citations
How to Cite
Magdalena Fidelis, Maria Wojcieszek, Katarzyna Gondek, Dominika Gacka, Agnieszka Zalewska, Aleksandra Mączyńska, Noor Alhuda Al-karawi, Paulina Kędziorek, & Zuzanna Tanç. (2026). ONE PATHWAY, INFINITE POTENTIAL? THE FUTURE OF GLP-1 THERAPIES: A 2026 CLINICAL UPDATE. International Journal of Innovative Technologies in Social Science, (1(49). https://doi.org/10.31435/ijitss.1(49).2026.4980

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