Effects of incretin drugs on glycemic control and body weight
https://doi.org/10.62751/2713-0177-2025-6-3-07
Abstract
Impaired effects of incretin hormones are the leading cause of type 2 diabetes mellitus (T2DM) and obesity. Currently, the most effective groups of drugs for the treatment of both T2DM and obesity are glucagon-like peptide-1 receptor agonists (semaglutide, liraglutide, etc.) and dual glucose-dependent insulinotropic polypeptide / glucagon-like peptide-1 receptor agonists (tirzepatide). Tirzepatide is the most effective in terms of glycemic control and weight loss, followed by semaglutide and liraglutide.
About the Authors
A. N. Levitskaya
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Anastasiya N. Levitskaya – assistant at the Department of endocrinology of the Faculty of general medicine
Moscow
T. Yu. Demidova
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Yu. Demidova – D. Sci. (Med.), Prof., Head of the Department of Endocrinology, Institute of Clinical Medicine
Scopus Author ID: 7003771623
Moscow
K. G. Lobanova
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Kristina G. Lobanova – C. Sci. (Med.), assistant at the Department of Endocrinology, Institute of Clinical Medicine
Moscow
References
1. Rabbani N, Thornalley PJ. Unraveling the impaired incretin effect in obesity and type 2 diabetes: Key role of hyperglycemia-induced unscheduled glycolysis and glycolytic overload. Diabetes Res Clin Pract. 2024;217:111905. doi: 10.1016/j.diabres.2024.111905.
2. Caruso I, Cignarelli A, Sorice GP, Perrini S, Giorgino F. Incretin-based therapies for the treatment of obesity-related diseases. NPJ Metab Health Dis. 2024;2(1):31. doi: 10.1038/s44324-024-00030-5
3. Schwartz SS, Epstein S, Corkey BE, Grant SFA, Gavin Iii JR, Aguilar RB, Herman ME. A unified pathophysiological construct of diabetes and its complications. Trends Endocrinol Metab. 2017;28(9):645–55. doi: 10.1016/j.tem.2017.05.005.
4. Nauck MA, Muller TD. Incretin hormones and type 2 diabetes. Diabetologia. 2023;66(10):1780–95. doi: 10.1007/s00125-023-05956-x.
5. Calanna S, Christensen M, Holst JJ, Laferrere B, Gluud LL, Vilsboll T, Knop FK. Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: Systematic review and meta-analyses of clinical studies. Diabetologia. 2013;56(5):965–72. doi: 10.1007/s00125-013-2841-0.
6. Faerch K, Torekov SS, Vistisen D, Johansen NB, Witte DR, Jonsson A et al. GLP-1 response to oral glucose is reduced in prediabetes, screen-detected type 2 diabetes, and obesity and influenced by sex: The ADDITION-PRO study. Diabetes. 2015;64(7):2513–25. doi: 10.2337/db14-1751.
7. Holst JJ, Rosenkilde MM. GIP as a therapeutic target in diabetes and obesity: Insight from incretin co-agonists. J Clin Endocrinol Metab. 2020;105(8):e2710–16. doi: 10.1210/clinem/dgaa327.
8. Bagger JI, Grøndahl MFG, Lund A, Holst JJ, Vilsboll T, Knop FK. Glucagonostatic potency of GLP-1 in patients with type 2 diabetes, patients with type 1 diabetes, and healthy control subjects. Diabetes. 2021;70(6):1347–56. doi: 10.2337/db20-0998.
9. Michałowska J, Miller-Kasprzak E, Bogdanski P. Incretin hormones in obesity and related cardiometabolic disorders: The clinical perspective. Nutrients. 2021;13(2):351. doi: 10.3390/nu13020351.
10. Gilbert MP, Pratley RE. GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: Review of head-to-head clinical trials. Front Endocrinol (Lausanne). 2020;11:178. doi: 10.3389/fendo.2020.00178.
11. Liu QK. Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists. Front Endocrinol (Lausanne). 2024;15:1431292. doi: 10.3389/fendo.2024.1431292.
12. Nauck MA, D'Alessio DA. 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. Cardiovasc Diabetol. 2022;21(1):169. doi: 10.1186/s12933-022-01604-7.
13. Knop FK, Aaboe K, Vilsboll T, Volund A, Holst JJ, Krarup T, Madsbad S. Impaired incretin eff and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab. 2012;14(6):500–10. doi: 10.1111/j.1463-1326.2011.01549.x.
14. Calanna S, Christensen M, Holst JJ, Laferrere B, Gluud LL, Vilsboll T, Knop FK. Secretion of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes: Systematic review and meta-analysis of clinical studies. Diabetes Care. 2013;36(10):3346–52. doi: 10.2337/dc13-0465.
15. Andreasen CR, Andersen A, Vilsboll T. The future of incretins in the treatment of obesity and non-alcoholic fatty liver disease. Diabetologia. 2023;66(10):1846–58. doi: 10.1007/s00125-023-05966-9.
16. Petri KCC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. Diabetes Obes Metab. 2018;20(9):2238–45. doi: 10.1111/dom.13358.
17. Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C et al. A randomized, controlled trial of liraglutide for adolescents with obesity. N Engl J Med. 2020;382(22):2117–28. doi: 10.1056/NEJMoa1916038.
18. Gabery S, Salinas CG, Paulsen SJ, Ahnfelt-Rønne J, Alanentalo T, Baquero AF et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020;5(6):e133429. doi: 10.1172/jci.insight.133429.
19. Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018;18:3–14. doi: 10.1016/j.molmet.2018.09.009.
20. Novikoff A, O'Brien SL, Bernecker M, Grandl G, Kleinert M, Knerr PJ et al. Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor monoand dual-agonists. Mol Metab. 2021;49:101181. doi: 10.1016/j.molmet.2021.101181.
21. Frias JP, Bastyr EJ 3rd, Vignati L, Tschop MH, Schmitt C, Owen K et al. The sustained effects of a dual GIP/GLP-1 receptor agonist, NNC00902746, in patients with type 2 diabetes. Cell Metab. 2017;26(2):343–52.e2. doi: 10.1016/j.cmet.2017.07.011.
22. Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: A randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392(10160):2180–93. doi: 10.1016/S0140-6736(18)32260-8.
23. Frías JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK et al.; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503–15. doi: 10.1056/NEJMoa2107519.
24. Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ et al. 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. Lancet Diabetes Endocrinol. 2022;10(6):418–29. doi: 10.1016/S2213-8587(22)00085-7.
25. Davidson MB, Bate G, Kirkpatrick P. Exenatide. Nat Rev Drug Discov. 2005;4(9):713–14. doi: 10.1038/nrd1828.
26. Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C et al. DURATION-5: Exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96(5):1301–10. doi: 10.1210/jc.2010-2081.
27. Buse JB, Nauck M, Forst T, Sheu WH, Shenouda SK, Heilmann CR et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): A randomised, open-label study. Lancet. 2013;381(9861):117–24. doi: 10.1016/S0140-6736(12)61267-7.
28. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: A 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009;374(9683):39–47. doi: 10.1016/S0140-6736(09)60659-0.
29. Pratley RE, Nauck MA, Barnett AH, Feinglos MN, Ovalle F, Harman-Boehm I et al. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): A randomised, open-label, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol. 2014;2(4):289–97. doi: 10.1016/S2213-8587(13)70214-6.
30. Dungan KM, Povedano ST, Forst T, Gonzalez JG, Atisso C, Sealls W, Fahrbach JL. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): A randomised, open-label, phase 3, non-inferiority trial. Lancet. 2014;384(9951):1349–57. doi: 10.1016/S0140-6736(14)60976-4.
31. Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbøl JD, Hansen T, Bain SC. 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. Lancet Diabetes Endocrinol. 2017;5(4):251–60. doi: 10.1016/S2213-8587(17)30013-X
32. Capehorn MS, Catarig AM, Furberg JK, Janez A, Price HC, Tadayon S et al. Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes Metab. 2020;46(2):100–9. doi: 10.1016/j.diabet.2019.101117.
33. Jung HN, Jung CH. The upcoming weekly tides (semaglutide vs. tirzepatide) against obesity: STEP or SURPASS? J Obes Metab Syndr. 2022;31(1):28–36. doi: 10.7570/jomes22012.
34. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205– 16. doi: 10.1056/NEJMoa2206038.
35. Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909–18. doi: 10.1038/s41591-023-02597-w.
36. Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38–48. doi: 10.1001/jama.2023.24945.
37. Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D et al. 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 Lond Engl. 2023;402(10402):613–26. doi: 10.1016/S0140-6736(23)01200-X.
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For citations:
Levitskaya A.N., Demidova T.Yu., Lobanova K.G. Effects of incretin drugs on glycemic control and body weight. FOCUS. Endocrinology. 2025;6(3):67-76. (In Russ.) https://doi.org/10.62751/2713-0177-2025-6-3-07
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