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GLP-1 Analogues as a Complementary Therapy in Patients after Metabolic Surgery: a Systematic Review and Qualitative Synthesis

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Abstract

The evidence is strong that bariatric surgery is superior to medical treatment in terms of weight loss and comorbidities in patients with severe obesity. However, a considerable part of patients presents with unsatisfactory response in the long term. It remains unclear whether postoperative administration of glucagon-like peptide-1 analogues can promote additional benefits. Therefore, a systematic review of the current literature on the management of postoperative GLP-1 analogue usage after metabolic surgery was performed. From 4663 identified articles, 6 met the inclusion criteria, but only one was a randomized controlled trial. The papers reviewed revealed that GLP-1 analogues may have beneficial effects on additional weight loss and T2D remission postoperatively. Thus, the use of GLP-1 analogues in addition to surgery promises good results concerning weight loss and improvements of comorbidities and can be used in patients with unsatisfactory results after bariatric surgery.

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References

  1. Sjöström L, Peltonen M, Jacobson P, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA - J Am Med Assoc [Internet]. 2014 Jun 11 [cited 2018 Oct 17];311(22):2297–304. Available from: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.5988

  2. Adams TD, Davidson LE, Litwin SE, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med [Internet]. 2017 Sep 21 [cited 2018 Oct 17];377(12):1143–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28930514

  3. Peterli R, Wölnerhanssen BK, Peters T, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss in patients with morbid obesity. JAMA [Internet]. 2018 Jan 16 [cited 2018 Dec 3];319(3):255. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29340679

  4. Cefalu WT, Rubino F, Cummings DE. Metabolic surgery for type 2 diabetes: changing the landscape of diabetes care. Diabetes Care. 2016;39(6):857–60.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rubino F, Nathan DM, Eckel RH, et al. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by International Diabetes Organizations. Obes Surg [Internet]. 2017 Jan 12 [cited 2018 Dec 3];27(1):2–21. Available from: http://link.springer.com/10.1007/s11695-016-2457-9

  6. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med [Internet]. 2015 Jul 2 [cited 2018 Oct 17];373(1):11–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26132939

  7. Astrup A, Rössner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009;374(9701):1606–16.

    Article  CAS  PubMed  Google Scholar 

  8. Torgerson JS, Hauptman J, Boldrin MN, et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155–61.

    Article  CAS  PubMed  Google Scholar 

  9. Falkén Y, Hellström PM, Holst JJ, et al. Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides. J Clin Endocrinol Metab. 2011;96(7):2227–35.

    Article  PubMed  Google Scholar 

  10. Baggio LL, Drucker DJ. Biology of Incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–57.

    Article  CAS  PubMed  Google Scholar 

  11. Ross SA, Dupre J. Effects of ingestion of triglyceride or galactose on secretion of gastric inhibitory polypeptide and on responses to intravenous glucose in normal and diabetic subjects. Diabetes [Internet]. 1978 Mar [cited 2019 Dec 20];27(3):327–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/640238

  12. Tolhurst G, Reimann F, Gribble FM. Intestinal sensing of nutrients. Handb Exp Pharmacol [Internet]. 2012 [cited 2019 Dec 20];209(209):309–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22249821

  13. Vilsbøll T. On the role of the incretin hormones GIP and GLP-1 in the pathogenesis of type 2 diabetes mellitus. Dan Med Bull [Internet]. 2004 Nov [cited 2019 Dec 20];51(4):364–70. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16009062

  14. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409–39.

    Article  CAS  PubMed  Google Scholar 

  15. Hare KJ, Vilsbøll T, Asmar M, et al. The glucagonostatic and insulinotropic effects of glucagon-like peptide 1 contribute equally to its glucose-lowering action. Diabetes. 2010;59(7):1765–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Meier | December ; J. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Publ Gr [Internet]. 2012 [cited 2020 Apr 28];8:728–42. Available from: www.nature.com/nrendo

  17. Muscogiuri G, DeFronzo RA, Gastaldelli A, et al. Glucagon-like peptide-1 and the central/peripheral nervous system: crosstalk in diabetes. Trends Endocrinol Metab. Elsevier Inc. 2017;28:88–103.

  18. Turton MD, O’Shea D, Gunn I, et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996;379(6560):69–72.

    Article  CAS  PubMed  Google Scholar 

  19. Rüttimann EB, Arnold M, Hillebrand JJ, et al.. Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms. Endocrinology [Internet]. 2009 Mar 1 [cited 2020 Apr 29];150(3):1174–81. Available from: https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2008-1221

  20. Petrie JR. The cardiovascular safety of incretin-based therapies: a review of the evidence [Internet]. Cardiovasc Diabetol. 2013;12 [cited 2020 Apr 29]. Available from: http://www.cardiab.com/content/12/1/130

  21. Boyle JG, Livingstone R, Petrie JR. Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: s comparative review. Clin Sci [Internet]. 2018 [cited 2020 Apr 29];132(15):1699–709. https://doi.org/10.1042/CS20171299.

    Article  CAS  Google Scholar 

  22. Muskiet MHA, Tonneijck L, Smits MM, et al. GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nat Rev Nephrol. Nat Publ Group. 2017;13:605–28.

  23. Luque MA, González N, Márquez L, et al. Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes. J Endocrinol. 2002;173(3):465–73.

    Article  CAS  PubMed  Google Scholar 

  24. Ruiz-Grande C, Alarcón C, Mérida E, et al. Lipolytic action of glucagon-like peptides in isolated rat adipocytes. Peptides. 1992;13(1):13–6.

    Article  CAS  PubMed  Google Scholar 

  25. Villanueva-Peñcarrillo ML, Márquez L, González N, et al. Effect of GLP-1 on lipid metabolism in human adipocytes. Horm Metab Res. 2001;33(2):73–7.

    Article  Google Scholar 

  26. Bifari F, Manfrini R, Dei Cas M, et al. Multiple target tissue effects of GLP-1 analogues on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Pharmacol Res. Academic Press. 2018;137:219–29.

  27. Jun LS, Millican RL, Hawkins ED, et al. Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production. Diabetes. 2015;64(3):819–27.

    Article  CAS  PubMed  Google Scholar 

  28. Zhou JY, Poudel A, Welchko R, et al. Liraglutide improves insulin sensitivity in high fat diet induced diabetic mice through multiple pathways. Eur J Pharmacol. 2019;15:861.

    Google Scholar 

  29. DeFronzo RA, Okerson T, Viswanathan P, et al.. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: A randomized, cross-over study. Curr Med Res Opin [Internet]. 2008 [cited 2020 Apr 29];24(10):2943–52. Available from: https://www.tandfonline.com/doi/full/10.1185/03007990802418851

  30. Tack CJ, Jacob S, Desouza C, et al. Long-term efficacy and safety of combined insulin and glucagon-like peptide-1 therapy: evidence from the LEADER trial. Diabetes Obes Metab. 2019;21(11):2450–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes - 5-year outcomes. N Engl J Med [Internet]. 2017 Feb 16 [cited 2018 Oct 17];376(7):641–51. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1600869

  32. Cotugno M, Nosso G, Saldalamacchia G, et al. Clinical efficacy of bariatric surgery versus liraglutide in patients with type 2 diabetes and severe obesity: a 12-month retrospective evaluation. Acta Diabetol [Internet]. 2014 Apr 14 [cited 2018 Oct 17];52(2):331–6. Available from: http://link.springer.com/10.1007/s00592-014-0644-5

  33. Yong W, Shibo W, Jingang L. Remission of insulin resistance in type 2 diabetic patients after gastric bypass surgery or exenatide therapy. Obes Surg. 2012 Jul;22(7):1060–7.

    Article  PubMed  Google Scholar 

  34. Shimizu H, Annaberdyev S, Motamarry I, et al.. Revisional bariatric surgery for unsuccessful weight loss and complications. Obes Surg [Internet]. 2013 Nov 5 [cited 2018 Jun 19];23(11):1766–73. Available from: http://link.springer.com/10.1007/s11695-013-1012-1

  35. Qiu J, Lundberg PW, Javier Birriel T, et al.. Revisional bariatric surgery for weight regain and refractory complications in a single MBSAQIP accredited center: what are we dealing with? Obes Surg [Internet]. 2018 Apr 20 [cited 2018 May 29]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/29679337

  36. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6

  37. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6

  38. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52(6):377–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Miras AD, Pérez-Pevida B, Aldhwayan M, et al. Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(7):549–59.

    Article  CAS  Google Scholar 

  40. Suliman M, Buckley A, Al Tikriti A, et al. Routine clinical use of liraglutide 3 mg for the treatment of obesity: outcomes in non-surgical and bariatric surgery patients. Diabetes Obes Metab. 2019;21(6):1498–501.

    Article  CAS  PubMed  Google Scholar 

  41. Gorgojo-Martínez JJ, Feo-Ortega G, Serrano-Moreno C. Effectiveness and tolerability of liraglutide in patients with type 2 diabetes mellitus and obesity after bariatric surgery. Surg Obes Relat Dis [Internet]. 2016 Dec [cited 2018 Sep 3];12(10):1856–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27256860

  42. Pajecki D, Halpern A, Cercato C, et al. Tratamento de curto prazo com liraglutide no reganho de peso após cirurgia bariátrica. Rev Col Bras Cir [Internet]. 2013 [cited 2018 Oct 17];40(3):191–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23912365

  43. Rye P, Modi R, Cawsey S, et al.. Efficacy of high-fose liraglutide as an adjunct for weight loss in patients with prior bariatric surgery. Obes Surg [Internet]. 2018 Jul 19 [cited 2018 Sep 3];28(11):3553–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30022424

  44. Wharton S, Kuk JL, Luszczynski M, et al. Liraglutide 3.0 mg for the management of insufficient weight loss or excessive weight regain post-bariatric surgery. Clin Obes. 2019;9(4):1–6.

    Article  Google Scholar 

  45. Yu J, Zhou X, Li L, et al. The long-term effects of bariatric surgery for type 2 diabetes: systematic review and meta-analysis of randomized and non-randomized evidence. Obes Surg. 2015;25(1):143–58.

    Article  PubMed  Google Scholar 

  46. Shukla AP, He D, Saunders KH, et al. Current concepts in management of weight regain following bariatric surgery. Expert Rev Endocrinol Metab [Internet]. 2018 Mar 4 [cited 2018 Aug 25];13(2):67–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30058859

  47. Degn KB, Juhl CB, Sturis J, et al. One week’s treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and-and-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004;53

  48. Werner U, Haschke G, Herling AW, et al. Pharmacological profile of lixisenatide: a new GLP-1 receptor agonist for the treatment of type 2 diabetes [Internet]. Vol. 164, Regulatory Peptides. 2010 [cited 2020 Apr 28]. p. 58–64. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20570597

  49. Linnebjerg H, Park S, Kothare PA, et al. Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes. Regul Pept. 2008;151(1–3):123–9.

    Article  CAS  PubMed  Google Scholar 

  50. Buse JB, Rosenstock J, Sesti G, 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.

    Article  CAS  PubMed  Google Scholar 

  51. Fineman MS, Bicsak TA, Shen LZ, et al. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care. 2003;26(8):2370–7.

    Article  CAS  PubMed  Google Scholar 

  52. Christensen M, Knop FK, Holst JJ, et al. Lixisenatide, a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. IDrugs. 2009;12:503–13.

    CAS  PubMed  Google Scholar 

  53. Matthews JE, Stewart MW, De Boever EH, et al. Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in patients with type 2 diabetes. J Clin Endocrinol Metab [Internet]. 2008 Dec [cited 2020 Apr 28];93(12):4810–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18812476

  54. Madsen K, Knudsen LB, Agersoe H, et al. Structure-activity and protraction relationship of long-acting glucagon-like peptide-1 derivatives: importance of fatty acid length, polarity, and bulkiness. J Med Chem. 2007;50(24):6126–32.

    Article  CAS  PubMed  Google Scholar 

  55. Rosenstock J, Raccah D, Koranyi L, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type2diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care. 2013;36(10):2945–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240–50.

    Article  CAS  PubMed  Google Scholar 

  57. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28(5):1083–91.

    Article  CAS  PubMed  Google Scholar 

  58. Marre M, Shaw J, Brändle M, et al. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med [Internet]. 2009 Mar [cited 2020 Apr 28];26(3):268–78. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19317822

  59. Blevins T, Pullman J, Malloy J, 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.

    Article  CAS  PubMed  Google Scholar 

  60. Umpierrez GE, Blevins T, Rosenstock J, et al. The effects of LY2189265, a long-acting glucagon-like peptide-1 analogue, in a randomized, placebo-controlled, double-blind study of overweight/obese patients with type 2 diabetes: the EGO study. Diabetes Obes Metab. 2011;13(5):418–25.

    Article  CAS  PubMed  Google Scholar 

  61. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2. Diabetes Care. 2005;28(5):1092–100.

    Article  CAS  PubMed  Google Scholar 

  62. Sharma D, Verma S, Vaidya S, et al. Recent updates on GLP-1 agonists: Current advancements & challenges. Biomed Pharmacother. Elsevier Masson SAS. 108, 2018:952–62.

  63. Lewis KD, Takenaka KY, Luber SD. Acute abdominal pain in the bariatric surgery patient. Emerg Med Clin North Am. W.B. Saunders. 2016;34:387–407.

  64. Kassir R, Debs T, Blanc P, et al. Complications of bariatric surgery: presentation and emergency management. Int J Surg. Elsevier Ltd. 2016;27:77–81.

  65. Aghajani E, Nergaard BJ, Leifson BG, et al.. The mesenteric defects in laparoscopic Roux-en-Y gastric bypass: 5 years follow-up of non-closure versus closure using the stapler technique. Surg Endosc [Internet]. 2017 [cited 2019 Dec 23];31(9):3743–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28205037

  66. Genco A, Soricelli E, Casella G, et al. Gastroesophageal reflux disease and Barrett’s esophagus after laparoscopic sleeve gastrectomy: a possible, underestimated long-term complication. Surg Obes Relat Dis. 2017;13(4):568–74.

    Article  PubMed  Google Scholar 

  67. Soricelli E, Casella G, Baglio G, et al. Lack of correlation between gastroesophageal reflux disease symptoms and esophageal lesions after sleeve gastrectomy. Surg Obes Relat Dis. 2018;14(6):751–6.

    Article  PubMed  Google Scholar 

  68. Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. Elsevier GmbH. 2019;30:72–130.

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  1. Romano Schneider and Marko Kraljević Contributed equally and share first authorship.

Authors and Affiliations

  1. Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, P.O. BOX, CH-4002, Basel, Switzerland

    Romano Schneider, Marko Kraljević, Ralph Peterli, Jennifer M. Klasen & Tarik Delko

  2. Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel, CH-4031, Basel, Switzerland

    Theresa V. Rohm & Claudia Cavelti-Weder

  3. Department of Biomedicine, University of Basel, University Hospital Basel, CH-4031, Basel, Switzerland

    Theresa V. Rohm & Claudia Cavelti-Weder

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Conflict of Interest

Dr. Schneider reports grants from the University of Basel, grants from Department of Surgery, University Hospital Basel, grants from SFCS, grants from Freiwillige Akademische Gesellschaft Basel, and grants from Gebauer Stiftung, outside the submitted work. Dr. Peterli reports grants and other from the Johnson & Johnson, outside the submitted work. Marko Kraljević, Theresa V. Rohm, Jennifer M. Klasen, Claudia Cavelti-Weder, and Tarik Delko have no conflicts of interest or financial ties to disclose. All authors have no ties to GLP-1 analogues producing pharmaceutical companies.

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Schneider, R., Kraljević, M., Peterli, R. et al. GLP-1 Analogues as a Complementary Therapy in Patients after Metabolic Surgery: a Systematic Review and Qualitative Synthesis. OBES SURG 30, 3561–3569 (2020). https://doi.org/10.1007/s11695-020-04750-7

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