Insights into the Efficacy of GLP-1 Agonists and Dual Agonists: Semaglutide and Tirzepatide in Obesity and Type 2 Diabetes
DOI:
https://doi.org/10.12775/QS.2024.35.56425Keywords
Semaglutide, tirzepatide, obesity, type 2 diabetesAbstract
The increasing global prevalence of obesity and type 2 diabetes (T2D) has prompted significant advancements in pharmacological treatments, with glucagon-like peptide-1 (GLP-1) receptor agonists and dual agonists representing key innovations. Semaglutide, a GLP-1 receptor agonist, and tirzepatide, a novel dual agonist targeting both GLP-1 and glucose-dependent insulinotropic peptide (GIP) receptors, have shown remarkable efficacy in improving glycemic control and promoting weight loss.
This review synthesizes the latest clinical evidence on the efficacy and safety of semaglutide and tirzepatide in the management of obesity and T2D, highlighting the findings from recent pivotal trials. In patients with T2D, semaglutide has consistently demonstrated superior glycemic control and weight loss compared to traditional therapies, as evidenced by the SUSTAIN trials [1]. Similarly, tirzepatide has emerged as a more efficacious option, with the SURPASS trials demonstrating greater reductions in HbA1c and more substantial weight loss compared to semaglutide. This positions tirzepatide as a potential first-line therapy for T2D.[2].
Both therapies have shown a favorable safety profile, with gastrointestinal side effects being the most common, and cardiovascular benefits observed in both drug classes. Given their dual mechanism of action, tirzepatide has shown unique potential in addressing both glycemic control and obesity, with emerging evidence supporting its use in non-diabetic patients with obesity [3].This review highlights the potential of these agents to revolutionise the management of obesity and T2D, with tirzepatide emerging as a promising next-generation treatment for metabolic diseases.
References
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., Kushner, R. F., & STEP 1 Study Group (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England journal of medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMoa2032183
Frías, J. P., Davies, M. J., Rosenstock, J., Pérez Manghi, F. C., Fernández Landó, L., Bergman, B. K., Liu, B., Cui, X., Brown, K., & SURPASS-2 Investigators (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. The New England journal of medicine, 385(6), 503–515. https://doi.org/10.1056/NEJMoa2107519
Sinha, R., Papamargaritis, D., Sargeant, J. A., & Davies, M. J. (2023). Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. Journal of obesity & metabolic syndrome, 32(1), 25–45. https://doi.org/10.7570/jomes22067
Bergmann, N. C., Davies, M. J., Lingvay, I., & Knop, F. K. (2023). Semaglutide for the treatment of overweight and obesity: A review. Diabetes, obesity & metabolism, 25(1), 18–35. https://doi.org/10.1111/dom.14863
Garvey, W. T., Frias, J. P., Jastreboff, A. M., le Roux, C. W., Sattar, N., Aizenberg, D., Mao, H., Zhang, S., Ahmad, N. N., Bunck, M. C., Benabbad, I., Zhang, X. M., & SURMOUNT-2 investigators (2023). Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet (London, England), 402(10402), 613–626. https://doi.org/10.1016/S0140-6736(23)01200-X
Drucker, D. J. (2018). "Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1." Cell Metabolism, 27(4),740–756. https://doi.org/10.1016/j.cmet.2018.03.001.
Heise, T., Mari, A., DeVries, J. H., Urva, S., Li, J., Pratt, E. J., Coskun, T., Thomas, M. K., Mather, K. J., Haupt, A., & Milicevic, Z. (2022). Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. The lancet. Diabetes & endocrinology,10(6), 418–429. https://doi.org/10.1016/S2213-8587(22)00085-7
Mather, K. J., Mari, A., Heise, T., DeVries, J. H., Hua, M., Urva, S., Coskun, T., Haupt, A., Heine, R. J., Pratt, E., Thomas, M. K., & Milicevic, Z. (2024). Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test. The Journal of clinical endocrinology and metabolism, 109(12), 3046–3054. https://doi.org/10.1210/clinem/dgae319
Heise, T., DeVries, J. H., Urva, S., Li, J., Pratt, E. J., Thomas, M. K., Mather, K. J., Karanikas, C. A., Dunn, J., Haupt, A., Milicevic, Z., & Coskun, T. (2023). Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes. Diabetes care, 46(5), 998–1004. https://doi.org/10.2337/dc22-1710
Rubino, D., Abrahamsson, N., Davies, M., Hesse, D., Greenway, F. L., Jensen, C., Lingvay, I., Mosenzon, O., Rosenstock, J., Rubio, M. A., Rudofsky, G., Tadayon, S., Wadden, T. A., Dicker, D., & STEP 4 Investigators (2021). Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA, 325(14), 1414–1425. https://doi.org/10.1001/jama.2021.3224
Sorli, C., Harashima, S. I., Tsoukas, G. M., Unger, J., Karsbøl, J. D., Hansen, T., & Bain, S. C. (2017). Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. The lancet. Diabetes & endocrinology, 5(4), 251–260. https://doi.org/10.1016/S2213-8587(17)30013-X
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., Woo, V., Hansen, O., Holst, A. G., Pettersson, J., Vilsbøll, T., & SUSTAIN-6 Investigators (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England journal of medicine, 375(19), 1834–1844. https://doi.org/10.1056/NEJMoa1607141
Rosenstock, J., Wysham, C., Frías, J. P., Kaneko, S., Lee, C. J., Fernández Landó, L., Mao, H., Cui, X., Karanikas, C. A., & Thieu, V. T. (2021). Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet (London, England), 398(10295), 143–155. https://doi.org/10.1016/S0140-6736(21)01324-6
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), 169. https://doi.org/10.1186/s12933-022-01604-7
Ludvik, B., Giorgino, F., Jódar, E., Frias, J. P., Fernández Landó, L., Brown, K., Bray, R., & Rodríguez, Á. (2021). Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): A randomised, open-label, parallel-group, phase 3 trial. Lancet (London, England), 398(10300), 583–598. https://doi.org/10.1016/S0140-6736(21)01443-4
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., Stefanski, A., & SURMOUNT-1 Investigators (2022). Tirzepatide Once Weekly for the Treatment of Obesity. The New England journal of medicine, 387(3), 205–216. https://doi.org/10.1056/NEJMoa2206038
Wharton, S., Calanna, S., Davies, M., Dicker, D., Goldman, B., Lingvay, I., Mosenzon, O., Rubino, D. M., Thomsen, M., Wadden, T. A., & Pedersen, S. D. (2022). Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Diabetes, obesity & metabolism, 24(1), 94–105. https://doi.org/10.1111/dom.14551
U.S. Food and Drug Administration. (2021). Semaglutide Injection for Type 2 Diabetes and Obesity. Retrieved from https://www.fda.gov
Bezin, J., Gouverneur, A., Pénichon, M., Mathieu, C., Garrel, R., Hillaire-Buys, D., Pariente, A., & Faillie, J. L. (2023). GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes care, 46(2), 384–390. https://doi.org/10.2337/dc22-1148
Aroda, V. R., Erhan, U., Jelnes, P., Meier, J. J., Abildlund, M. T., Pratley, R., Vilsbøll, T., & Husain, M. (2023). Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes. Diabetes, obesity & metabolism, 25(5), 1385–1397. https://doi.org/10.1111/dom.14990
Novo Nordisk. (n.d.). Ozempic® (semaglutide) injection, for subcutaneous use. Full prescribing information. Retrieved from https://www.novonordiskforyou.com
Petri, K. C. C., Ingwersen, S. H., Flint, A., Zacho, J., & Overgaard, R. V. (2018). Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. Diabetes, obesity & metabolism, 20(9), 2238–2245. https://doi.org/10.1111/dom.13358
Zhang, R., Hou, Q. C., Li, B. H., Deng, L., Yang, Y. M., Li, T. X., Yao, X. Q., Yang, L. L., Lin, X. L., Liao, Y. Q., Wang, L., Liu, Y. P., Tan, J., Wan, Z. W., & Shuai, P. (2023). Efficacy and safety of subcutaneous semaglutide in adults with overweight or obese: a subgroup meta-analysis of randomized controlled trials. Frontiers in endocrinology, 14, 1132004. https://doi.org/10.3389/fendo.2023.1132004
Kelly, M. S., Scopelliti, E. M., Goodson, K. E., Lo, C. M. A., Nguyen, H. X., & Simon, B. (2024). Real-world evaluation of the effects of tirzepatide in patients with type 2 diabetes mellitus. Diabetes, obesity & metabolism, 26(12), 5661–5668. https://doi.org/10.1111/dom.15934
France, N. L., & Syed, Y. Y. (2024). Tirzepatide: A Review in Type 2 Diabetes. Drugs, 84(2), 227–238. https://doi.org/10.1007/s40265-023-01992-4
Del Prato, S., Kahn, S. E., Pavo, I., Weerakkody, G. J., Yang, Z., Doupis, J., Aizenberg, D., Wynne, A. G., Riesmeyer, J. S., Heine, R. J., Wiese, R. J., & SURPASS-4 Investigators (2021). Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet (London, England), 398(10313), 1811–1824. https://doi.org/10.1016/S0140-6736(21)02188-7
Dahl, D., Onishi, Y., Norwood, P., Huh, R., Bray, R., Patel, H., & Rodríguez, Á. (2022). Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA, 327(6), 534–545. https://doi.org/10.1001/jama.2022.0078
Blüher, M., Aras, M., Aronne, L. J., Batterham, R. L., Giorgino, F., Ji, L., Pietiläinen, K. H., Schnell, O., Tonchevska, E., & Wilding, J. P. H. (2023). New insights into the treatment of obesity. Diabetes, obesity & metabolism, 25(8), 2058–2072. https://doi.org/10.1111/dom.15077
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Laura Opalska, Adrianna Muciek, Martyna Mocarska, Anna Orłowska, Katarzyna Strakowska, Anna Maryńczak, Jan Mencel, Nicole Nitschke
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 182
Number of citations: 0
