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Review of Advances in Anti-obesity Pharmacotherapy: Implications for a Multimodal Treatment Approach with Metabolic Surgery

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Abstract

There is a growing need for treatments for patients who would benefit from further weight loss following bariatric surgery or weight loss maintenance/long-term disease remission. Currently, therapeutic options are limited. Although largely dismissed previously, advances in weight loss pharmacotherapy now offer the possibility of achieving clinically significant weight loss. Historical comparisons drawn between the effects of medications vs surgery are generally inaccurate as novel classes of anti-obesity pharmacotherapy have since been developed and moreover, reflect an outdated approach in comparing medicine with surgery. Herein, we provide an overview of the most recently developed anti-obesity medications which may not only present a potentially innovative approach to medical treatment of obesity but may also inspire renewed enthusiasm for investigating what can be achieved through multimodal care.

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References

  1. Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish Obese subjects. N Engl J Med. 2007;357(8):741–52.

    Article  PubMed  Google Scholar 

  2. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):74–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Franz MJ. Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. J Acad Nutr Diet. 2015;115(9):1447–63.

    Article  PubMed  Google Scholar 

  4. Drucker DJ, Philippe J, Mojsov S, et al. Glucagon-like peptide 1 stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A. 1987;84(10):3434–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nauck MA, Heimesaat MM, Behle K, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycaemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab. 2002;87(2):1239–46.

    Article  CAS  PubMed  Google Scholar 

  6. Navarro M, De Fonseca R, Alvarez E, et al. Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake. J Neruochem. 1996;67(5):1982–91.

    Article  CAS  Google Scholar 

  7. Pournaras DJ, Osborne A, Hawkins SC, et al. Remission of type 2 diabetes after gastric bypass and banding: mechanisms and two year outcomes. Ann Surg. 2010;252(6):966–71.

    Article  PubMed  Google Scholar 

  8. Pournaras DJ, Aasheim ET, Bueter M, et al. Effect of bypassing the proximal gut on gut hormones involved with glycemic control and weight loss. Surg Obes Relat Dis. 2012;8(4):371–4.

    Article  PubMed  Google Scholar 

  9. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomised, controlled trial of 3.0mg of liraglutide in weight management. N Engl J Med. 2015;373(7):11–22.

    Article  PubMed  CAS  Google Scholar 

  10. Fujikoa K, O’Neil P, Davies M, et al. Early weight loss with liraglutide 3.0mg predicts 1-year weight loss and is associated with improvements in clinical markers. Obesity. 2016;24(11):2278–88.

    Article  CAS  Google Scholar 

  11. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy vs 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.

    Article  CAS  PubMed  Google Scholar 

  13. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44.

    Article  CAS  PubMed  Google Scholar 

  14. O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose ranging, phase 2 trial. Lancet. 2018;392(10148):637–49.

    Article  PubMed  Google Scholar 

  15. Ben-Menachem E, Axelsen M, Johanson EH, et al. Predictors of weight loss in adults with topiramate-treated epilepsy. Obesity. 2012;11(4):556–62.

    Article  Google Scholar 

  16. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–52.

    Article  CAS  PubMed  Google Scholar 

  17. Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomised, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297–308.

    Article  CAS  PubMed  Google Scholar 

  18. Gustafson A, King C, Rey JA. Lorcaserin (Belviq): a selective serotonin 5-HT2C agonist in the treatment of obesity. PT. 2013;38(9):525–34.

    Google Scholar 

  19. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245–56.

    Article  CAS  PubMed  Google Scholar 

  20. Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96(10):3067–77.

    Article  CAS  PubMed  Google Scholar 

  21. Bohula EA, Wiviott SD, McGuire DK, et al. Cardiovascular safety of lorcaserin in overweight or obese patients. N Engl J Med. 2018;379(12):1107–17.

    Article  CAS  PubMed  Google Scholar 

  22. Rothman RB, Baumann MH, Savage JE, et al. Evidence for possible involvement of 5-HT(2B) in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000;102(23):2836–41.

    Article  CAS  PubMed  Google Scholar 

  23. Greenway FL, Whitehouse MJ, Guttadauria M, et al. Rational design of a combination medication for the treatment of obesity. Obesity. 2008;17(1):30–9.

    Article  PubMed  CAS  Google Scholar 

  24. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/ bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013;21(5):935–43.

    Article  CAS  PubMed  Google Scholar 

  25. Nissen SE, Wolski KE, Prcela L, et al. Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomised clinical trial. JAMA. 2016;315(10):990–1004.

    Article  CAS  PubMed  Google Scholar 

  26. Bays HE, Weinstein R, Law G, et al. Canagliflozin: Effects in overweight and obese subjects without diabetes mellitus. Obesity. 2014;22(4):1042–9.

    Article  CAS  PubMed  Google Scholar 

  27. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342–62.

    Article  CAS  PubMed  Google Scholar 

  28. Malin SK, Kashyap SR. Effects of metformin on weight loss. Curr Opin Endocrinol Diabetes Obes. 2014;21(10):323–9.

    Article  CAS  PubMed  Google Scholar 

  29. Goudswaard AN, Furlong NJ, Rutten GE, et al. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;18(4):CD003418.

    Google Scholar 

  30. Diabetes Prevention Programme Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Programme Outcomes Study. Lancet. 2009;374(9702):1677–86.

    Article  Google Scholar 

  31. Colquitt JL, Pickett K, Loveman E, et al. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014;8:CD003641.

    Google Scholar 

  32. Hutcheon DA, Hale AL, Ewing JA, et al. Short-term preoperative weight loss and postoperative outcomes in bariatric surgery. J Am Coll Surg. 2018;226(4):514–24.

    Article  PubMed  Google Scholar 

  33. Malone M, Alger-Mayer SA, Lindstrom J. Use of orlistat 60 mg in the management of weight loss before bariatric surgery. Ann Pharmacother. 2012;46(6):779–84.

    Article  PubMed  CAS  Google Scholar 

  34. Guisado-Macias JA, Mendez-Sanchez F, Baltasar-Tello I, et al. Fluoxetine, topiramate, and combination of both to stabilize eating behaviour before bariatric surgery. Actas Esp Psiquiatr. 2016;44(3):93–6.

    PubMed  Google Scholar 

  35. Aberle J, Freier A, Busch P, et al. Treatment with sibutramine prior to Roux-en-Y gastric bypass leads to an improvement of metabolic parameters and to a reduction of liver size and operative time. Obes Surg. 2009;19(11):1504–7.

    Article  PubMed  Google Scholar 

  36. Ard JD, Beavers DP, Hale E, et al. Use of phentermine/topiramate extended release in combination with sleeve gastrectomy in patients with BMI 50kg/m2 or more. Surg Obes Relat Dis. 2019; Article in press available from https://www.soard.org/article/S1550-7289(19)30159-5/abstract. Accessed 4/6/19

  37. King WC, Hinerman AS, Belle SH, et al. Comparison of the performance of common measures of weight regain after bariatric surgery for association with clinical outcomes. JAMA. 2018;320(15):1560–9.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Brethauer SA, Kothari S, Sudan R, et al. Systematic review on reoperative bariatric surgery: American Society for Metabolic and Bariatric Surgery Revision Task Force. Surg Obes Relat Dis. 2014;10(5):952–72.

    Article  PubMed  Google Scholar 

  39. Stanford FC, Alfaris N, Gomez G, et al. The utility of weight loss medications after bariatric surgery for weight regain or inadequate weight loss: a multi-centre study. Surg Obes Relat Dis. 2017;13(3):491–500.

    Article  PubMed  Google Scholar 

  40. Nor-Hanipah Z, Nasr EC, Bucak E, et al. Efficacy of adjuvant weight loss medication after bariatric surgery. Surg Obes Relat Dis. 2018;14(1):93–8.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Gorgojo-Martinez J, 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. 2016;12(10):1856–65.

    Article  PubMed  Google Scholar 

  43. Shehadeh N, Zaid WA, Zuckerman Levin N, et al. Liraglutide treatment in post-bariatric surgery patients who failed to maintain weight reduction. Surg Obes Relat Dis. 2017;13(10):S144.

    Article  Google Scholar 

  44. Pajecki D, Halpern A, Cercato C, et al. Short-term use of liraglutide in the management of patients with weight regain after bariatric surgery. Rev Col Bras Cir. 2013;40(5):191–5.

    Article  PubMed  Google Scholar 

  45. Rye P, Modi R, Cawsey S, et al. Efficacy of high-dose liraglutide as an adjunct for weight loss in patients with prior bariatric surgery. Obes Surg. 2018;28(11):3553–8.

    Article  PubMed  Google Scholar 

  46. Shwartz J, Chaudhry UI, Suzo A, et al. Pharmacotherapy in conjunction with a diet and exercise program for the treatment of weight recidivism or weight loss plateau post-bariatric surgery: a retrospective review. Obes Surg. 2016;26(2):452–8.

    Article  Google Scholar 

  47. Jester L, Wittgrove AC, Clark W. Adjunctive use of appetite suppressant medications for improved weight management in bariatric surgical patients. Obes Surg. 1996;6(5):412–5.

    Article  CAS  PubMed  Google Scholar 

  48. Zilberstein B, Pajecki D. Garcia de Brito A, Gallafrio ST, Eshkenazy R, Andrade CG. Topiramate after adjustable gastric banding in patients with binge eating and difficulty losing weight. Obes Surg. 2004;14(6):802–5.

    Article  PubMed  Google Scholar 

  49. Toth AT, Gomez G, Shukla A, et al. Weight loss medications in young adults after bariatric surgery for weight regain or inadequate weight loss: a multi-centre study. Children. 2018;5(9)

    Article  PubMed Central  Google Scholar 

  50. Zoss I, Piec G, Horber FF. Impact of orlistat therapy on weight reduction in morbidly obese patients after implantation of the Swedish adjustable gastric band. Obes Surg. 2002;12(1):113–7.

    Article  PubMed  Google Scholar 

  51. Stanford FC, Toth AT, Shukla AP, et al. Weight loss medications in older adults after bariatric surgery for weight regain or inadequate weight loss: a multicentre study. Bariatr Surg Pract Patient Care. 2018;13(4):171–8.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Creange C, Lin E, Ren-Fielding C, et al. Use of liraglutide for weight loss in patients with prior bariatric surgery. Surg Obes Relat Dis. 2016;12(7):S157.

    Google Scholar 

  53. Gutt S, Schraier S, Gonzalez Bagnes MF, et al. Long-term pharmacotherapy of obesity in patients that have undergone bariatric surgery: pharmacological prevention and management of body weight regain. Expert Opin Pharmacother. 2019;20(8):393–947.

    Article  CAS  Google Scholar 

  54. Hanjieva-Darlenska T, Handjiev S, Larsen TM, et al. Initial weight loss on an 800-kcal diet as a predictor of weight loss success after 8 weeks: the Diogenes study. Eur J Clin Nutr. 2010;64(9):994–9.

    Article  Google Scholar 

  55. Rissanen A, Lean M, Rössner S, et al. Predictive value of early weight loss in obesity management with orlistat: an evidence-based assessment of prescribing guidelines. Int J Obes Relat Metab Disord. 2003;27(1):103–9.

    Article  CAS  PubMed  Google Scholar 

  56. Fujioka K, Plodkowski R, O’Neil PM, et al. The relationship between early and weight loss at 1 year with naltrexone ER/bupropion ER combination therapy. Int J Obes. 2016;40(9):1369–75.

    Article  CAS  Google Scholar 

  57. Patel DK, Stanford FC. Safety and tolerability of new-generation anti-obesity medications: a narrative review. Postgrad Med. 2018;130(2):173–82.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Welbourn R, le Roux C, Owen-Smith A, et al. Why the NHS should do more bariatric surgery; how much should we do? BMJ. 2016;353:i1472.

    Article  PubMed  Google Scholar 

  59. Baker C. Obesity statistics. House of Commons Library Briefing Paper No 3336; 2018. https://researchbriefings.parliament.uk/ResearchBriefing/Summary/SN03336. Accessed 4/6/19

  60. Xia Y, Kelton CM, Guo JJ, et al. Treatment of obesity: pharmacotherapy trends in the United States from 1999-2010. Obesity. 2015;23(8):1721–8.

    Article  PubMed  Google Scholar 

  61. Thomas CE, Mauer EA, Shukla AP, et al. Low adoption of weight loss medications: a comparison of prescribing patterns of antiobesity pharmacotherapies and SGLT2s. Obesity. 2016;24(9):1955–61.

    Article  PubMed  Google Scholar 

  62. Pournaras DJ, le Roux CW. Type 2 diabetes: multimodal treatment of a complex disease. Lancet. 2015;386(9):936–37.

    Article  Google Scholar 

  63. Gesquiere I, Steenackers N, Lannoo M, et al. Predicting iron absorption from an effervescent iron supplement in obese patients before and after Roux-en-Y gastric bypass: a preliminary study. J Trace Elem Med Biol. 2019;52(3):68–73.

    Article  CAS  PubMed  Google Scholar 

  64. Arzan C, Porat D, Fine-Shamir N, et al. Oral levothyroxine therapy post bariatric surgery: biopharmaceutical aspects and clinical effects. Surg Obes Relat Dis. 2019;15(2):333–41.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Upper GI Surgery, Southmead Hospital, Bristol, UK

    Alexis C Sudlow & Dimitri J Pournaras

  2. Department of Experimental Pathology, University College Dublin, Dublin, Ireland

    Carel W le Roux

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  1. Alexis C Sudlow
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  2. Carel W le Roux
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  3. Dimitri J Pournaras
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Correspondence to Dimitri J Pournaras.

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This article does not contain any studies with human participants or animals performed by any of the authors. For this type of study, informed consent is not required and does not apply to our work.

Conflict of Interest

ACS has no conflict of interest to declare. CWlR reports grants from Science Foundation Ireland, grants from Health Research Board, grants from AnaBio during the conduct of the study; other from NovoNordisk, other from GI Dynamics, personal fees from Eli Lilly, grants and personal fees from Johnson and Johnson, personal fees from Sanofi Aventis, personal fees from Astra Zeneca, personal fees from Janssen, personal fees from Bristol-Myers Squibb, personal fees from Boehringer-Ingelheim, outside the submitted work and shares in Keyron. DJP reports receiving honoraria from NovoNordisk and Johnson and Johnson for lectures.

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C Sudlow, A., W le Roux, C. & J Pournaras, D. Review of Advances in Anti-obesity Pharmacotherapy: Implications for a Multimodal Treatment Approach with Metabolic Surgery. OBES SURG 29, 4095–4104 (2019). https://doi.org/10.1007/s11695-019-04206-7

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