Obesity Surgery

, Volume 28, Issue 3, pp 615–626 | Cite as

A Meta-Analysis of GLP-1 After Roux-En-Y Gastric Bypass: Impact of Surgical Technique and Measurement Strategy

  • Pichamol Jirapinyo
  • David X. Jin
  • Taha Qazi
  • Nitin Mishra
  • Christopher C. ThompsonEmail author
Original Contributions



Roux-en-Y gastric bypass (RYGB) is an effective treatment for diabetes. Glucagon-like peptide-1 (GLP-1) is a gut hormone that is important to glucose homeostasis.


This study aimed to assess GLP-1 level and its predictors after RYGB.


The study design was a meta-analysis. The data sources were MEDLINE, EMBASE, Web of Science, and the Cochrane Databases. The study selection composed of studies with pre- and post-RYGB levels. The main outcomes were as follows: Primary outcome was the change in postprandial GLP-1 levels after RYGB. Secondary outcomes included the changes in fasting glucose, fasting insulin, and fasting GLP-1 levels after RYGB. Meta-regression to determine predictors of changes in GLP-1 levels was performed. Outcomes were reported using Hedge’s g.


Twenty-four studies with 368 patients were included. Postprandial GLP-1 levels increased after RYGB (Hedge’s g = 1.29, p < 0.0001), while fasting GLP-1 did not change (p = 0.23). Peak postprandial GLP-1 levels gave the most consistent results (I 2 = 9.11). Fasting glucose and insulin levels decreased after RYGB (p < 0.0001).

Roux limb length was a significant predictor for amount of GLP-1 increase (β = − 0.01, p = 0.02). Diabetes status, amount of weight loss, length of biliopancreatic limb, and time of measurement were not significant predictors (p > 0.05).


Postprandial GLP-1 levels increase after RYGB, while fasting levels remain unchanged. Shorter Roux limb length is associated with greater increase in postprandial GLP-1, which may lead to better glycemic control in this population.


RYGB GLP-1 Incretin Diabetes Metabolic Bariatric Mechanism Obesity 



Roux-En-Y Gastric Bypass


Glucagon-Like Peptide-1


Body Mass Index


Non-alcoholic Fatty Liver Disease


United States


Swedish Obese Subjects


Type 2 Diabetes Mellitus


Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently


Area Under The Curve


Oral Glucose Tolerance Test


Risk Of Bias In Non-Randomized Studies—Of Interventions


Newcastle-Ottawa Quality Assessment Scale


Confidence Interval


Randomized Controlled Trial


Farnesoid X Receptor



No financial or material support was received for this research project.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval Statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent Statement

Does not apply.


  1. 1.
    WHO | Obesity and overweight. WHO n.d. Accessed 16 Aug 2016.
  2. 2.
    Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: United States, 2011-2014. NCHS Data Brief. 2015:1–8.Google Scholar
  3. 3.
    Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. J Health Econ. 2012;31:219–30. Scholar
  4. 4.
    Mason EE, Ito C. Gastric bypass in obesity. Surg Clin North Am. 1967;47:1345–51.CrossRefPubMedGoogle Scholar
  5. 5.
    Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741–52. Scholar
  6. 6.
    Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med. 2014;370:2002–13. Scholar
  7. 7.
    Mason EE. The mechanisms of surgical treatment of type 2 diabetes. Obes Surg. 2005;15:459–61. Scholar
  8. 8.
    Meek CL, Lewis HB, Reimann F, et al. The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones. Peptides. 2016;77:28–37. Scholar
  9. 9.
    Anderwald C-H, Tura A, Promintzer-Schifferl M, et al. Alterations in gastrointestinal, endocrine, and metabolic processes after bariatric Roux-en-Y gastric bypass surgery. Diabetes Care. 2012;35:2580–7. Scholar
  10. 10.
    Borg C, le Roux C, Ghatei M, et al. Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety. Br J Surg. 2006;93:210–5. Scholar
  11. 11.
    Bose M, Teixeira J, Olivan B, et al. Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery. J Diabetes. 2010;2:47–55. Scholar
  12. 12.
    Breitman I, Saraf N, Kakade M, et al. The effects of an amino acid supplement on glucose homeostasis, inflammatory markers, and incretins after laparoscopic gastric bypass. J Am Coll Surg. 2011;212:617–25. Scholar
  13. 13.
    Bryant EJ, King NA, Falken Y, et al. Relationships among tonic and episodic aspects of motivation to eat, gut peptides, and weight before and after bariatric surgery. Surg Obes Relat Dis. 2013;9:802–8. Scholar
  14. 14.
    Campos GM, Rabl C, Peeva S, et al. Improvement in peripheral glucose uptake after gastric bypass surgery is observed only after substantial weight loss has occurred and correlates with the magnitude of weight lost. J Gastrointest Surg. 2010;14:15–22. Scholar
  15. 15.
    Chronaiou A, Tsoli M, Kehagias I, et al. Lower ghrelin levels and exaggerated postprandial peptide-YY, glucagon-like peptide-1, and insulin responses, after gastric fundus resection, in patients undergoing Roux-en-Y gastric bypass: a randomized clinical trial. Obes Surg. 2012;22:1761–70. Scholar
  16. 16.
    Evans S, Pamuklar Z, Rosko J, et al. Gastric bypass surgery restores meal stimulation of the anorexigenic gut hormones glucagon-like peptide-1 and peptide YY independently of caloric restriction. Surg Endosc Interv Tech. 2012;26:1086–94. Scholar
  17. 17.
    Falken Y, Hellstrom 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;96:2227–35. Scholar
  18. 18.
    Fellici AC, Lambert G, Lima MMO, et al. Surgical treatment of type 2 diabetes in subjects with mild obesity: mechanisms underlying metabolic improvements. Obes Surg. 2015;25:36–44. Scholar
  19. 19.
    Gandolfini M-P, Coupaye M, Bouaziz E, et al. Cardiovascular changes after gastric bypass surgery: involvement of increased secretions of glucagon-like peptide-1 and brain natriuretic peptide. Obes Surg. 2015;25:1933–9. Scholar
  20. 20.
    Hansen EN, Tamboli RA, Isbell JM, et al. Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery. Am J Physiol-Gastrointest LIVER Physiol. 2011;300:G795–802. Scholar
  21. 21.
    Jorgensen NB, Jacobsen SH, Dirksen C, et al. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with type 2 diabetes and normal glucose tolerance. Am J Physiol-Endocrinol Metab. 2012;303:E122–31. Scholar
  22. 22.
    Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes. 2009;33:786–95. Scholar
  23. 23.
    Lips MA, de Groot GH, van Klinken JB, et al. Calorie restriction is a major determinant of the short-term metabolic effects of gastric bypass surgery in obese type 2 diabetic patients. Clin Endocrinol. 2014;80:834–42. Scholar
  24. 24.
    Morinigo R, Lacy AM, Casamitjana R, et al. GLP-1 and changes in glucose tolerance following gastric bypass surgery in morbidly obese subjects. Obes Surg. 2006;16:1594–601. Scholar
  25. 25.
    Nosso G, Griffo E, Cotugno M, et al. Comparative effects of Roux-en-Y gastric bypass and sleeve gastrectomy on glucose homeostasis and incretin hormones in obese type 2 diabetic patients: a one-year prospective study. Horm Metab Res. 2016;48:312–7. Scholar
  26. 26.
    O’Brien CS, Wang G, McGinty J, et al. Effects of gastrogastric fistula repair on weight loss and gut hormone levels. Obes Surg. 2013;23:1294–301. Scholar
  27. 27.
    Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22:740–8. Scholar
  28. 28.
    Promintzer-Schifferl M, Prager G, Anderwald C, et al. Effects of gastric bypass surgery on insulin resistance and insulin secretion in nondiabetic obese patients. Obesity. 2011;19:1420–6. Scholar
  29. 29.
    Rubino F, Gagner M, Gentileschi P, et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240:236–42. Scholar
  30. 30.
    Salinari S, Bertuzzi A, Guidone C, et al. Insulin sensitivity and secretion changes after gastric bypass in normotolerant and diabetic obese subjects. Ann Surg. 2013;257:462–8. Scholar
  31. 31.
    Samat A, Malin SK, Huang H, et al. Ghrelin suppression is associated with weight loss and insulin action following gastric bypass surgery at 12 months in obese adults with type 2 diabetes. Diabetes Obes Metab. 2013;15:963–6. Scholar
  32. 32.
    Steven S, Hollingsworth KG, Small PK, et al. Weight loss decreases excess pancreatic triacylglycerol specifically in type 2 diabetes. Diabetes Care. 2016;39:158–65. Scholar
  33. 33.
    Umeda LM, Silva EA, Carneiro G, et al. Early improvement in glycemic control after bariatric surgery and its relationships with insulin, GLP-1, and glucagon secretion in type 2 diabetic patients. Obes Surg. 2011;21:896–901. Scholar
  34. 34.
    Yan W, Polidori D, Yieh L, et al. Effects of meal size on the release of GLP-1 and PYY after Roux-en-Y gastric bypass surgery in obese subjects with or without type 2 diabetes. Obes Surg. 2014;24:1969–74. Scholar
  35. 35.
    Yip S, Signal M, Smith G, et al. Lower glycemic fluctuations early after bariatric surgery partially explained by caloric restriction. Obes Surg. 2014;24:62–70. Scholar
  36. 36.
    Yousseif A, Emmanuel J, Karra E, et al. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans. Obes Surg. 2014;24:241–52. Scholar
  37. 37.
    Zhang X, Cheng Z, Xiao Z, et al. Comparison of short- and mid-term efficacy and the mechanisms of gastric bypass surgeries on managing obese and nonobese type 2 diabetes mellitus: a prospective study. Arch Med Res. 2015;46:303–9. Scholar
  38. 38.
    Laferrere B. Effect of gastric bypass surgery on the incretins. Diabetes Metab. 2009;35:513–7.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Nausheen S, Shah IH, Pezeshki A, et al. Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats. Am J Physiol Endocrinol Metab. 2013;305:E507–18. Scholar
  40. 40.
    Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244:741–9. Scholar
  41. 41.
    Penney NC, Kinross J, Newton RC, et al. The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review. Int J Obes. 2015;39:1565–74. Scholar
  42. 42.
    Kohli R, Bradley D, Setchell KD, et al. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab. 2013;98:E708–12. Scholar
  43. 43.
    Ahmad NN, Pfalzer A, Kaplan LM. Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity. Int J Obes. 2013;37:1553–9. Scholar
  44. 44.
    Gerhard GS, Styer AM, Wood GC, et al. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care. 2013;36:1859–64. Scholar
  45. 45.
    Gleysteen JJ. Five-year outcome with gastric bypass: Roux limb length makes a difference. Surg Obes Relat Dis Off J Am Soc Bariatr Surg. 2009;5:242–247; discussion 247-249. Scholar
  46. 46.
    Stefanidis D, Kuwada TS, Gersin KS. The importance of the length of the limbs for gastric bypass patients—an evidence-based review. Obes Surg. 2011;21:119–24. Scholar
  47. 47.
    Orci L, Chilcott M, Huber O. Short versus long Roux-limb length in Roux-en-Y gastric bypass surgery for the treatment of morbid and super obesity: a systematic review of the literature. Obes Surg. 2011;21:797–804. Scholar
  48. 48.
    Dogan K, Homan J, Aarts EO, et al. A short or a long Roux limb in gastric bypass surgery: does it matter? Surg Endosc. 2016;
  49. 49.
    Kaska L, Kobiela J, Proczko M, et al. Does the length of the biliary limb influence medium-term laboratory remission of type 2 diabetes mellitus after Roux-en-Y gastric bypass in morbidly obese patients? Wideochirurgia Inne Tech Małoinwazyjne Videosurgery Miniinvasive Tech Kwart Pod Patronatem Sekc Wideochirurgii TChP Oraz Sekc Chir Bariatrycznej TChP. 2014;9:31–9. Scholar
  50. 50.
    Gupta RVN, Chamany T, Makam R. Does length of common limb influence remission of diabetes? Short-term results. J Minimal Access Surg. 2016;12:54–7. Scholar
  51. 51.
    Dutra RA, Araújo WM, de Andrade JI. The effects of Roux-en-Y limb length on gastric emptying and enterogastric reflux in rats. Acta Cirúrgica Bras Soc Bras Para Desenvolv Pesqui Em Cir. 2008;23:179–83.Google Scholar
  52. 52.
    Le Blanc-Louvry I, Ducrotté P, Lemeland JF, et al. Motility in the Roux-Y limb after distal gastrectomy: relation to the length of the limb and the afferent duodenojejunal segment—an experimental study. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 1999;11:365–74.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Pichamol Jirapinyo
    • 1
  • David X. Jin
    • 1
  • Taha Qazi
    • 1
  • Nitin Mishra
    • 2
  • Christopher C. Thompson
    • 1
    Email author
  1. 1.Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women’s HospitalBostonUSA
  2. 2.Department of SurgeryMayo Clinic HospitalPhoenixUSA

Personalised recommendations