The “relay approach” in obesity management: From incretin mimetics to bariatric surgery and back to pharmacotherapy

This publication is dedicated to the rationale and implementation in clinical practice of a management strategy for obesity, considered as a chronic, multifactorial, and relapsing disease. The main objective of the article is to propose to the medical community the concept of the “relay approach”, which is designed to replace the traditional opposition of conservative and surgical treatment methods with the principle of their synergistic and sequential application. The authors analyze the biological mechanisms of metabolic adaptation and neurohormonal weight defense, explaining the inevitability of relapses with short-term interventions and dictating the need for continuous patient management. The article details scenarios for the use of “second-generation” incretin mimetics. Clear criteria are proposed for initiating therapy with the GLP-1 RA semaglutide, and the tactic of timely treatment escalation – transitioning to the more effective dual GIP/GLP-1 receptor agonist tirzepatide upon reaching a plateau or a suboptimal response – is justified. A new paradigm is taken into account: the integration of pharmacotherapy with bariatric surgery. The article reveals the role of pharmacotherapy as a “bridge therapy” to reduce surgical risks in patients with severe obesity and as a “reverse relay” tool for the treatment of postoperative weight regain. Separate sections are devoted to optimizing patient conditions in specific clinical situations, including preconception and orthopedic preparation, as well as achieving remission of obstructive sleep apnea syndrome. A differentiated approach is formulated for type 2 diabetes mellitus: a “dual-target strategy” is articulated, taking into account not only weight-reducing efficacy but also economic cost-effectiveness and the organ-protective properties of the medications. This article represents a comprehensive guide aimed at forming multidisciplinary teams to ensure long-term control over the patient’s metabolic health and achieve sustained remission of associated complications.

1. Dedov II, Mokrysheva NG, Melnichenko GA, Troshina EA, Mazurina NV, Ershova EV et al. Clinical recommendations «Gestational diabetes mellitus» of the Russian Ministry of Health. Version of the year 2024. Bulletin of Reproductive Health. 2025;4(2):14–30. (In Russ.) https://doi.org/10.14341/brh12763.

2. Драпкина ОМ, Самородская ИВ, Старинская МА, Ким ОТ, Неймарк АЕ. Ожирение: оценка и тактика ведения пациентов. М.; 2021. 174 с.

3. Pantelis AG, Lapatsanis DP. Metabolic bariatric surgery in face of new antiobesity medications-10 + 1 challenges. Metab Target Organ Damage. 2023;3:17. https://doi.org/10.20517/mtod.2023.27.

4. Bray GA, Heisel WE, Afshin A, Jensen MD, Dietz WH, Long M et al. The Science of Obesity Management: An Endocrine Society Scientific Statement. Endocr Rev. 2018;39(2):79–132. https://doi.org/10.1210/er.2017-00253.

5. Laddu D, Neeland IJ, Carnethon M, Stanford FC, Mongraw-Chaffin M, Barone Gibbs B et al. Implementation of Obesity Science Into Clinical Practice: A Scientific Statement From the American Heart Association. Circulation. 2024;150(1):e7–e19. https://doi.org/10.1161/CIR.0000000000001221.

6. Cohen RV, Prager G, le Roux CW, Lingvay I, Salminen P. International Federation for the Surgery of Obesity statement on metabolic bariatric surgery after pharmacotherapy-induced weight loss in clinical obesity. Lancet Diabetes Endocrinol. 2025;13(9):733–736. https://doi.org/10.1016/S2213-8587(25)00198-6.

7. Christoffersen BØ, Sanchez-Delgado G, John LM, Ryan DH, Raun K, Ravussin E. Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss. Obesity. 2022;30:841–857. https://doi.org/10.1002/oby.23374.

8. Tuccinardi D, Masi D, Watanabe M, Zanghi Buffi V, De Domenico F, Berti S et al. Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan. J Endocrinol Invest. 2025;48:2761–2798. https://doi.org/10.1007/s40618-025-02700-7.

9. Sattar N, Buse JB. Why Early, Large-scale Weight Loss Is the Future of Type 2 Diabetes Care. Diabetes Care. 2026;49(5):695–705. https://doi.org/10.2337/dci25-0069.

10. Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study. Obesity. 2014;22(1):5–13. https://doi.org/10.1002/oby.20662.

11. Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2016;4(11):913–921. https://doi.org/10.1016/S2213-8587(16)30162-0.

12. Frias-Toral E, Chapela S, Gonzalez V, Martinuzzi A, Locatelli J, Llobera N et al. Optimizing Nutritional Management Before and After Bariatric Surgery: A Comprehensive Guide for Sustained Weight Loss and Metabolic Health. Nutrients. 2025;17(4):688. https://doi.org/10.3390/nu17040688.

13. Harper ME, Dent RRM, McPherson R. High-Quality Weight Loss in Obesity: Importance of Skeletal Muscle. Diabetes. 2025;74(12):2191–2198. https://doi.org/10.2337/dbi25-0003.

14. Kommu S, Berg RL. Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus-A systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2024;25(9):e13792. https://doi.org/10.1111/obr.13792.

15. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I et al.; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002. https://doi.org/10.1056/NEJMoa2032183.

16. Salukhov VV, Galstyan GR, Khalimov YuSh, Bakulin IG, Cherkashin DV, Shadrichev FE, Sukhotskaia NA. Practical application of semaglutide: From evidence-based research to expert decisions. Meditsinskiy Sovet. 2025;19(6):14–29. (In Russ.) https://doi.org/10.21518/ms2025-185.

17. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221–2232. https://doi.org/10.1056/NEJMoa2307563.

18. Friedman CA. A review of metabolic health outcomes of tirzepatide vs semaglutide in obesity and type 2 diabetes. URNCST J. 2025:9(10):1–6. https://doi.org/10.26685/urncst.945

19. El K, Douros JD, Willard FS, Novikoff A, Sargsyan A, Perez-Tilve D et al. The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets. Nature Metabolism. 2023;5(6):945–954. https://doi.org/10.1038/s42255-023-00811-0.

20. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B et al.; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205–216. https://doi.org/10.1056/NEJMoa2206038.

21. Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E et al.; SURMOUNT-5 Trial Investigators. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26–36. https://doi.org/10.1056/NEJMoa2416394.

22. Psaltis JP, Marathe JA, Nguyen MT, Le R, Bursill CA, Marathe CS et al. Incretin-based therapies for the management of cardiometabolic disease in the clinic: past, present and future. Med Res Rev. 2025;45:29–65. https://doi.org/10.1002/med.22070.

23. Mamas MA, Bays H, Li R, Upadhyay N, Irani T, Senyucel C et al. Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial. Eur Heart J Open. 2025;5(5):oeaf117. https://doi.org/10.1093/ehjopen/oeaf117.

24. Gasoyan H, Schulte R, Boyer CB, Casacchia NJ, Butsch WS, Le P et al. Obesity Treatments and Weight Changes in Clinical Practice After Discontinuation of Semaglutide or Tirzepatide. Diabetes Obes Metab. 2026. https://doi.org/10.1111/dom.70660.

25. Gorgojo-Martínez JJ. Adipocentric Strategy for the Treatment of Type 2 Diabetes Mellitus. J Clin Med. 2025;14(3):678. https://doi.org/10.3390/jcm14030678.

26. Barrett TS, Hafermann JO, Richards S, LeJeune K, Eid GM. Obesity T reatment With Bariatric Surgery vs GLP-1 Receptor Agonists. JAMA Surg. 2025;160(11):1232–1239. https://doi.org/10.1001/jamasurg.2025.3590.

27. Obermark AD, Seo DY, Bernazard A, Richards JR, Phillippe S, Khorgami Z, Chow GS. Bariatric outcomes of high BMI patients with preoperative antiobesity medications. Surg Endosc. 2025;39(9):6061–6068. https://doi.org/10.1007/s00464-025-11851-w.

28. Brown A, Patel S, Vu AH, Somoza E, Mei T, Jenkins M et al. RZY8JY68MG Comparative effectiveness of semaglutide and tirzepatide vs bariatric surgery. Surg Obes Relat Dis. 2025;21(6 Suppl.):S1. https://doi.org/10.1016/j.soard.2025.04.008.

29. Salminen P, Kow L, Aminian A, Kaplan LM, Nimeri A, Prager G et al. IFSO Consensus on Definitions and Clinical Practice Guidelines for Obesity Management-an International Delphi Study. Obes Surg. 2024;34(1):30–42. https://doi.org/10.1007/s11695-023-06913-8.

30. Çalık Başaran N, Dotan I, Dicker D. Post metabolic bariatric surgery weight regain: the importance of GLP-1 levels. Int J Obes. 2025;49(3):412–417. https://doi.org/10.1038/s41366-024-01461-2.

31. Cohen RV, Park JY, Prager G, Bueter M, le Roux CW, Parmar C et al. Role of obesity-management medications before and after metabolic bariatric surgery: a systematic review. Br J Surg. 2024;111(12):znae284. https://doi.org/10.1093/bjs/znae284.

32. Cohen RV, Busetto L, Levinson R, Le Roux CW, Salminen P, Prager G; International Consensus on the Role of Obesity Management Medications in the Context of Metabolic Bariatric Surgery. International consensus position statement on the role of obesity management medications in the context of metabolic bariatric surgery: expert guideline by the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). Br J Surg. 2024;111(12):znae283. https://doi.org/10.1093/bjs/znae283.

33. Mok J, Adeleke MO, Brown A, Magee CG, Firman C, Makahamadze C et al. Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery: The BARI-OPTIMISE Randomized Clinical Trial. JAMA Surg. 2023;158(10):1003–1011. https://doi.org/10.1001/jamasurg.2023.2930.

34. Tan YW, Shang M, Davis S, Gananadha S. GLP-1 receptor agonists as an to bariatric surgery for weight loss and metabolic outcome improvement: a systematic review and meta-analysis. Langenbecks Arch Surg. 2025;410(1):295. https://doi.org/10.1007/s00423-025-03831-4.

35. Kim M, Mehta H, Alexander C, Schweitzer M, Lewis S. PNDM9V5MLB Use of glucagon-like peptide 1 agonists (GLP-1’s) among individuals undergoing bariatric surgery in the United States: a retrospective cohort study. Surg Obes Relat Dis. 2025;21(6 Suppl.):S70. https://doi.org/10.1016/j.soard.2025.04.214.

36. Neimark AE, Lapshina SE. Current trends in bariatric surgery. Russian Surgical Journal. 2025;2(2):103–111. (In Russ.) https://doi.org/10.18705/3034-7270-2025-1-2-103-111.

37. Grandone I, Nannipieri M, Conte C, Cava E, Schiavo L. Preoperative weight loss by noninvasive approach in patients with obesity scheduled for bariatric and metabolic surgery: an update narrative review of indications and results available until 2024. Updates Surg. 2025;77(7):1985–1999. https://doi.org/10.1007/s13304-025-02198-x.

38. Cunningham JG, Szoka N, Tabone LE, Cox S, Aylward L, Abunnaja S. Preoperative and early adjuvant weight loss medications in bariatric surgery patients with body mass index over 60 or suboptimal initial response to surgery. Surg Obes Relat Dis. 2023;19(8):832–840. https://doi.org/10.1016/j.soard.2023.01.021.

39. Mathur V, Wasden K, Shin TH, Medhati P, Nimeri AA, Tavakkoli A, Sheu EG. Neoadjuvant Semaglutide, Bariatric Surgery Weight Loss, and Overall Outcomes. JAMA Surg. 2025;160(5):594–596. https://doi.org/10.1001/jamasurg.2025.0001.

40. Sun Y, Liu B, Smith JK, Correia MLG, Jones DL, Zhu Z et al. Association of Preoperative Body Weight and Weight Loss With Risk of Death After Bariatric Surgery. JAMA Netw Open. 2020;3(5):e204803. https://doi.org/10.1001/jamanetworkopen.2020.4803.

41. Dahlgren N, Scott J, Langan E, Buccini P, Blackhurst D. 9BRA5GPAQN Bariatric surgery complications by BMI, a continued review and analysis of 2020–2023 National MBSAQIP Database. Surg Obes Relat Dis. 2025;21(6 Suppl.):S62. https://doi.org/10.1016/j.soard.2025.04.191.

42. Salukhov VV, Shchegolev AV, Surzhikov PV, Apostolidi EV, Prochik YaE. Preoperative management algorithm for endoscopic or surgical interventions in patients receiving incretin mimetics. Meditsinskiy Sovet. 2026;20. (In Russ.) https://doi.org/10.21518/ms2026-161. (In print).

43. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):503–515. https://doi.org/10.1056/NEJMoa2107519.

44. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834–1844. https://doi.org/10.1056/NEJMoa1607141.

45. Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109–121. https://doi.org/10.1056/NEJMoa2403347.

46. Reitzel SB, Bøgelund M, Basse A, Barszczewska O, Ren H. Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates. Curr Med Res Opin. 2023;39(8):1055–1060. https://doi.org/10.1080/03007995.2023.2231275.

47. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503–515. https://doi.org/10.1056/NEJMoa2107519.

48. Dedov II, Shestakova MV, Sukhareva OYu, Mokrysheva NG, Andreeva EN, Bezlepkina OB et al. Standards of Specialized Diabetes Care / Edited by Dedov I.I., Shestakova M.V., Sukhareva O.Yu. 12th Edition. Diabetes Mellitus. 2025;28(5S):1–175. (In Russ.) https://doi.org/10.14341/DM20255S.

49. Salukhov VV, Ilinskiy NS, Vasilev EV, Sardinov RT, Gladyshev DV. Possibilities of metabolic surgery for the treatment of type 2 diabetes mellitus in patients with grade 1 alimentary obesity. Diabetes Mellitus. 2018;21(1):15–25. (In Russ.) https://doi.org/10.14341/DM9292.

50. Markova TN, Subbotina LS, Markova KN. Pharmacological management of obesity in women during preconception care. RMJ. 2026;(3):30–36. (In Russ.) https://doi.org/10.32364/2225-2282-2026-3-5.

51. Imbroane MR, LeMoine F, Nau CT. Preconception glucagon-like peptide-1 receptor agonist use associated with decreased risk of adverse obstetrical outcomes. Am J Obstet Gynecol. 2025;233(2):116.e1–116.e7. https://doi.org/10.1016/j.ajog.2025.01.019.

52. Khan SS, Grobman WA, Kazi DS. Periconceptional Glucagon-Like Peptide-1 Receptor Agonist Use and Discontinuation. JAMA Cardiol. 2025;10(6):525–526. https://doi.org/10.1001/jamacardio.2025.0637.

53. Karonova TL, Nikulina AA, Murasheva AV, Tiselko AV, Chernikova AT, Shavinina AI, Sukhotskaya NA. Role of GLP-1 RA and GLP-1/GIP RA in comprehensive preconception preparation for women with obesity. RMJ. Medical Review. 2025;9(10):749–757. (In Russ.) https://doi.org/10.32364/2587-6821-2025-9-10-8.

54. Soliman AR, Magd Eldin Saleem H, El Meligi AAH, Naguib M, Sobh Mohamed R, Abdelaziz GR et al. Metabolic/bariatric surgery optimization: a position statement by Arabic association for the study of diabetes and metabolism (AASD). Diabetol Metab Syndr. 2025;17(1):37. https://doi.org/10.1186/s13098-024-01564-w.

55. Thomson F, White K, Robinson P, Gaston P, Clement N. Preoperative tirzepatide therapy in obese total hip arthroplasty candidates: a modelling study of cost and complication reduction. Orthop Procs. 2026;108-B(Suppl. 3):10–10. https://doi.org/10.1302/1358-992X.2026.3.010.

56. Cherkashin DV. Tirzepatide – alternative to CPAP-therapy or new opportunity in the therapy of obstructive sleep apnea? Meditsinskiy Sovet. 2025;19(23):114–122. (In Russ.) https://doi.org/10.21518/ms2025-551.

57. Karonova TL, Nikulina AA, Murasheva AV, Eganyan ShA, Tikhonov NI, Sukhotskaya NA, Grineva EN. New frontiers in obesity care: key updates from the American Association of Clinical Endocrinology International Recommendations for the diagnosis and treatment of adults with obesity. RMJ. 2026;(3):24–29. (In Russ.) https://doi.org/10.32364/2225-2282-2026-3-4.

58. Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024;391(13):1193–1205. https://doi.org/10.1056/NEJMoa2404881.

59. Malhotra A, Grunstein RR, Azarbarzin A, Sands SA, Dang X, Chakladar S et al. Tirzepatide for sleep-disordered breathing in SURMOUNT-OSA: Time course and association with body weight. Sleep Med. 2025;136:106853. https://doi.org/10.1016/j.sleep.2025.106853.