Impact GLP-1 Agonists Following Bariatric

NCT06132477 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2098885
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Glucagon-like peptide 1 (GLP-1) is a hormone that helps regulate blood glucose levels through improved insulin sensitivity and release of insulin from the pancreas, control hunger, induce satiety and plays a role in the metabolic health of a person. GLP-1 receptor agonists (GLP1-RAs) have been shown to be effective in achieving weight loss in patients with type 2 diabetes while improving blood glucose control. Bariatric surgical procedures have been shown to be effective in treating obesity as well as superior to best medical therapy for treatment of diabetes not just through restriction of calories but also through a positive impact in modifications of gut hormones, changes in circulating bile acids, modifications in the gut microflora as well as other undefined mechanisms. The combined benefits of GLP1-RAs with bariatric surgery have only been studied to a limited effect. In this randomized trial, the effects of continuation or discontinuation of GLP1-RA therapy in patients undergoing bariatric surgery will be determined. We will compare changes in weight, metabolic determinants including circulating bile acids and gut microbiome, psychological determinants of eating behavior, and adverse side effects in patients who continue vs discontinue therapy. Given differences in metabolic and clinical outcomes in patients undergoing vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB), both surgical groups will be examined. The study will be conducted at a high volume bariatric surgical program where patients will undergo randomization at the time of final clinic visit prior to surgery to continue or discontinue GLP1-RA. It is hypothesized that participants who continue GLP1-RA therapy after bariatric surgery will lose more weight with improved blood glucose control than those who discontinue therapy. Furthermore, changes in gut microbiome and circulating bile acids, known determinants of metabolic health, will be modified to a differential extent in those who are on GLP1-RAs vs those where GLP1-RAs are discontinued. Understanding the role these medications play in not only clinical outcomes after metabolic surgery but potential metabolic mechanisms by which surgery improves patient's metabolic health could help people with obesity and type 2 diabetes make informed decisions about their treatment options as well as advise providers on the continuation of these medications in the perioperative and postoperative period.

Conditions

Morbid Obesity; Metabolic Syndrome; Diabetes Mellitus; Hypertension; Obstructive Sleep Apnea of Adult

Keywords

glp-1 agonist; Morbid Obesity; Bariatric Surgery; Metabolic syndrome; Diabetes Mellitus; Hypertension; Obstructive Sleep Apnea

Outcome Measures

Primary Outcomes (5)

• Effect of GLP1-RA on weight loss

  To investigate the effects of GLP1-RAs on weight loss reflected as change in BMI (kg per meter sq) in patients undergoing metabolic surgery

  6 months

• Effect of GLP1-RA on circulating bile acids and metabolites

  Determine the impact of GLP1-RA on circulating bile acids and other metabolites

  6 months

• Effector of GLP1-RA on gut microbiome diversity

  To determine the impact of GLP1-RAs after bariatric surgery on changes in the gut microbiome

  6 months

• Effect of GLP1-RA on satiety and hunger

  To assess the impact of GLP-1 agonists on satiety and hunger in patients who undergo metabolic surgery. Scale will be a validated scoring system, "Daily Eats Questionnaire," with scores ranging from 0-10, with a 0 indicating no hunger, and 10 indicating extreme hunger

  6 months

• Effect of GLP1-RA on Glycemic control

  HGBA1C levels will be measured at 3 and 6 months after surgery to determine if HGBA1C drops more in patients maintained on GLP1-RA

  6 months

Study Arms (2)

GLP-1 Agonist Group

ACTIVE COMPARATOR

This cohort will consist of patients undergoing bariatric surgery who are currently receiving a GLP-1 Agonists for weight loss and/or diabetes management, that will be maintained on their preoperative dose of GLP-1 agonist following their bariatric surgery. This includes semaglutide, tirzepitide, among others. The dosage will be variable, but will be the same dose the patient is on prior to the bariatric surgery. Duration will be one of the aims of the study.

Drug: GLP-1 receptor agonist

Non-GLP-1 Agonist Group

NO INTERVENTION

This cohort will consist of patients undergoing bariatric surgery who are currently receiving a GLP-1 Agonist for weight loss and/or diabetes management that will be required to stop taking their preoperative dose of GLP-1 agonist following their bariatric surgery. Dosage preoperative will be variable based on what the patient is currently taking, as well as the medication being taken.

Interventions

GLP-1 receptor agonist DRUG

Randomized to continue or discontinue GLP-1 receptor agonists after bariatric surgery

Also known as: GLP-1 agonists

GLP-1 Agonist Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Greater than 18 years of age
• Participation in care by one of the surgeons at MU Health Care
• Undergoing surgical weight loss through the Weight Management and Metabolic Center
• Body mass index of 30-80 kg/m2
• Meet insurance criteria, as set forth by the patient's insurance policy, to qualify for coverage for weight loss surgery or as a self-pay patient for the weight loss procedure
• Planned laparoscopic Roux-en-Y gastric bypass, sleeve gastrectomy, revisional weight loss surgery, or duodenal switch or modification of. If patients are not willing to be randomized they will not be enrolled as randomized but can still participate having samples collected.
• Willingness to have blood collected before and after surgical procedure at defined points or at minimum have clinical data collected.
• Willingness to have clinical data entered into a prospective database
• Additional specimens collected as stated in the protocol will be offered but collection not mandated.
• \. Taking a GLP-1 agonist as part of their routine medical care apart from any planned surgical procedure. The current standard of care regarding continuation or discontinuation of GLP-1 agonists has not been established and is at the discretion of members of the patient's medical team but to be included the patient and medical care team must be willing to continue or discontinue the GLP-1 agonist after surgery depending on the randomized group.

You may not qualify if:

• Pregnant patient
• Desire to not participate
• Age less than 18
• Patient fails to fulfill insurance mandated criteria and is not interested in paying cash for their procedure
• Not taking a GLP-1 agonist as part of standard medical care
• Unwilling to follow-up at required postoperative visits
• Unwilling to stop GLP-1 agonist if randomized into group to stop GLP-1 agonist or unwilling to continue the GLP-1 agonist if randomized into that respective group. If chooses to continue or discontinue the medication apart from randomization the patient can still participate as a non-randomized participant

Sponsors & Collaborators

• University of Missouri-Columbia: lead
• American Society for Metabolic and Bariatric Surgery: collaborator

Study Sites (1)

University of Missouri Hospital

Columbia, Missouri, 65201, United States

RECRUITING

Related Publications (37)

• Lee SJ, Shin SW. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med. 2017 Apr 13;376(15):1491-2. doi: 10.1056/NEJMc1701944. No abstract available.

  PMID: 28406283 BACKGROUND

• Mouton AJ, Li X, Hall ME, Hall JE. Obesity, Hypertension, and Cardiac Dysfunction: Novel Roles of Immunometabolism in Macrophage Activation and Inflammation. Circ Res. 2020 Mar 13;126(6):789-806. doi: 10.1161/CIRCRESAHA.119.312321. Epub 2020 Mar 12.

  PMID: 32163341 BACKGROUND

• Zhang Y, Liu J, Yao J, Ji G, Qian L, Wang J, Zhang G, Tian J, Nie Y, Zhang YE, Gold MS, Liu Y. Obesity: pathophysiology and intervention. Nutrients. 2014 Nov 18;6(11):5153-83. doi: 10.3390/nu6115153.

  PMID: 25412152 BACKGROUND

• Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, Aminian A, Pothier CE, Kim ES, Nissen SE, Kashyap SR; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes. N Engl J Med. 2014 May 22;370(21):2002-13. doi: 10.1056/NEJMoa1401329. Epub 2014 Mar 31.

  PMID: 24679060 BACKGROUND

• Blond E, Disse E, Cuerq C, Drai J, Valette PJ, Laville M, Thivolet C, Simon C, Caussy C. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease in severely obese people: do they lead to over-referral? Diabetologia. 2017 Jul;60(7):1218-1222. doi: 10.1007/s00125-017-4264-9. Epub 2017 Mar 28.

  PMID: 28352941 BACKGROUND

• de Witte D, Wijngaarden LH, van Houten VAA, van den Dorpel MA, Bruning TA, van der Harst E, Klaassen RA, Niezen RA. Improvement of Cardiac Function After Roux-en-Y Gastric Bypass in Morbidly Obese Patients Without Cardiac History Measured by Cardiac MRI. Obes Surg. 2020 Jul;30(7):2475-2481. doi: 10.1007/s11695-020-04543-y.

  PMID: 32198618 BACKGROUND

• Schauer DP, Feigelson HS, Koebnick C, Caan B, Weinmann S, Leonard AC, Powers JD, Yenumula PR, Arterburn DE. Bariatric Surgery and the Risk of Cancer in a Large Multisite Cohort. Ann Surg. 2019 Jan;269(1):95-101. doi: 10.1097/SLA.0000000000002525.

  PMID: 28938270 BACKGROUND

• Pucci A, Batterham RL. Mechanisms underlying the weight loss effects of RYGB and SG: similar, yet different. J Endocrinol Invest. 2019 Feb;42(2):117-128. doi: 10.1007/s40618-018-0892-2. Epub 2018 May 5.

  PMID: 29730732 BACKGROUND

• Sakran N, Soifer K, Hod K, Sherf-Dagan S, Soued S, Kessler Y, Adelson D, Biton R, Buchwald JN, Goitein D, Raziel A. Long-term Reported Outcomes Following Primary Laparoscopic Sleeve Gastrectomy. Obes Surg. 2023 Jan;33(1):117-128. doi: 10.1007/s11695-022-06365-6. Epub 2022 Nov 28.

  PMID: 36441488 BACKGROUND

• Cooper TC, Simmons EB, Webb K, Burns JL, Kushner RF. Trends in Weight Regain Following Roux-en-Y Gastric Bypass (RYGB) Bariatric Surgery. Obes Surg. 2015 Aug;25(8):1474-81. doi: 10.1007/s11695-014-1560-z.

  PMID: 25595383 BACKGROUND

• Abel SA, English WJ, Duke MC, Williams DB, Aher CV, Broucek JR, Spann MD. Benefits of Adjuvant Medical Weight Loss Intervention in Setting of Weight Regain and Inadequate Weight Loss After Weight Loss Surgery. Am Surg. 2023 May;89(5):1857-1863. doi: 10.1177/00031348221078957. Epub 2022 Mar 22.

  PMID: 35317659 BACKGROUND

• Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, Hjerpsted JB. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017 Sep;19(9):1242-1251. doi: 10.1111/dom.12932. Epub 2017 May 5.

  PMID: 28266779 BACKGROUND

• Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, Niskanen L, Rasmussen MF, Rissanen A, Rossner S, Savolainen MJ, Van Gaal L; NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012 Jun;36(6):843-54. doi: 10.1038/ijo.2011.158. Epub 2011 Aug 16.

  PMID: 21844879 BACKGROUND

• Hindso M, Hedback N, Svane MS, Moller A, Martinussen C, Jorgensen NB, Dirksen C, Gasbjerg LS, Kristiansen VB, Hartmann B, Rosenkilde MM, Holst JJ, Madsbad S, Bojsen-Moller KN. The Importance of Endogenously Secreted GLP-1 and GIP for Postprandial Glucose Tolerance and beta-Cell Function After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy Surgery. Diabetes. 2023 Mar 1;72(3):336-347. doi: 10.2337/db22-0568.

  PMID: 36478039 BACKGROUND

• Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. doi: 10.4158/EP161365.GL. Epub 2016 May 24.

  PMID: 27219496 BACKGROUND

• Wirunsawanya K, Chittimoju S, Fantasia KL, Modzelewski KL, Steenkamp D, Alexanian SM. Insulin Requirements in Patients With Type 2 Diabetes Undergoing Bariatric Surgery in the Inpatient Setting and Upon Discharge: A Single-Center Retrospective Analysis of Insulin Management Strategies. Endocr Pract. 2021 Jun;27(6):538-544. doi: 10.1016/j.eprac.2020.12.014. Epub 2021 Jan 11.

  PMID: 34016530 BACKGROUND

• Sarma S, Palcu P. Weight loss between glucagon-like peptide-1 receptor agonists and bariatric surgery in adults with obesity: A systematic review and meta-analysis. Obesity (Silver Spring). 2022 Nov;30(11):2111-2121. doi: 10.1002/oby.23563.

  PMID: 36321278 BACKGROUND

• Jensen AB, Renstrom F, Aczel S, Folie P, Biraima-Steinemann M, Beuschlein F, Bilz S. Efficacy of the Glucagon-Like Peptide-1 Receptor Agonists Liraglutide and Semaglutide for the Treatment of Weight Regain After Bariatric surgery: a Retrospective Observational Study. Obes Surg. 2023 Apr;33(4):1017-1025. doi: 10.1007/s11695-023-06484-8. Epub 2023 Feb 11.

  PMID: 36765019 BACKGROUND

• Llewellyn DC, Logan Ellis H, Aylwin SJB, Ostarijas E, Green S, Sheridan W, Chew NWS, le Roux CW, Miras AD, Patel AG, Vincent RP, Dimitriadis GK. The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review. Obesity (Silver Spring). 2023 Jan;31(1):20-30. doi: 10.1002/oby.23600. Epub 2022 Dec 10.

  PMID: 36502288 BACKGROUND

• Guarino D, Moriconi D, Mari A, Rebelos E, Colligiani D, Baldi S, Anselmino M, Ferrannini E, Nannipieri M. Postprandial hypoglycaemia after Roux-en-Y gastric bypass in individuals with type 2 diabetes. Diabetologia. 2019 Jan;62(1):178-186. doi: 10.1007/s00125-018-4737-5. Epub 2018 Oct 12.

  PMID: 30315341 BACKGROUND

• Madsbad S. Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists. Diabetes Obes Metab. 2016 Apr;18(4):317-32. doi: 10.1111/dom.12596. Epub 2015 Dec 29.

  PMID: 26511102 BACKGROUND

• Hurtado A MD, Acosta A. Precision Medicine and Obesity. Gastroenterol Clin North Am. 2021 Mar;50(1):127-139. doi: 10.1016/j.gtc.2020.10.005. Epub 2021 Jan 5.

  PMID: 33518159 BACKGROUND

• de Vos WM, Tilg H, Van Hul M, Cani PD. Gut microbiome and health: mechanistic insights. Gut. 2022 May;71(5):1020-1032. doi: 10.1136/gutjnl-2021-326789. Epub 2022 Feb 1.

  PMID: 35105664 BACKGROUND

• Shapiro H, Kolodziejczyk AA, Halstuch D, Elinav E. Bile acids in glucose metabolism in health and disease. J Exp Med. 2018 Feb 5;215(2):383-396. doi: 10.1084/jem.20171965. Epub 2018 Jan 16.

  PMID: 29339445 BACKGROUND

• Jonsson I, Bojsen-Moller KN, Kristiansen VB, Veedfald S, Wewer Albrechtsen NJ, Clausen TR, Kuhre RE, Rehfeld JF, Holst JJ, Madsbad S, Svane MS. Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass. Front Endocrinol (Lausanne). 2021 May 14;12:681116. doi: 10.3389/fendo.2021.681116. eCollection 2021.

  PMID: 34084153 BACKGROUND

• Pournaras DJ, Glicksman C, Vincent RP, Kuganolipava S, Alaghband-Zadeh J, Mahon D, Bekker JH, Ghatei MA, Bloom SR, Walters JR, Welbourn R, le Roux CW. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology. 2012 Aug;153(8):3613-9. doi: 10.1210/en.2011-2145. Epub 2012 Jun 6.

  PMID: 22673227 BACKGROUND

• Chaudhari SN, Luo JN, Harris DA, Aliakbarian H, Yao L, Paik D, Subramaniam R, Adhikari AA, Vernon AH, Kilic A, Weiss ST, Huh JR, Sheu EG, Devlin AS. A microbial metabolite remodels the gut-liver axis following bariatric surgery. Cell Host Microbe. 2021 Mar 10;29(3):408-424.e7. doi: 10.1016/j.chom.2020.12.004. Epub 2021 Jan 11.

  PMID: 33434516 BACKGROUND

• Jendle J, Hyotylainen T, Oresic M, Nystrom T. Pharmacometabolomic profiles in type 2 diabetic subjects treated with liraglutide or glimepiride. Cardiovasc Diabetol. 2021 Dec 17;20(1):237. doi: 10.1186/s12933-021-01431-2.

  PMID: 34920733 BACKGROUND

• Madsen MSA, Holm JB, Palleja A, Wismann P, Fabricius K, Rigbolt K, Mikkelsen M, Sommer M, Jelsing J, Nielsen HB, Vrang N, Hansen HH. Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice. Sci Rep. 2019 Oct 30;9(1):15582. doi: 10.1038/s41598-019-52103-x.

  PMID: 31666597 BACKGROUND

• Ocana-Wilhelmi L, Martin-Nunez GM, Ruiz-Limon P, Alcaide J, Garcia-Fuentes E, Gutierrez-Repiso C, Tinahones FJ, Moreno-Indias I. Gut Microbiota Metabolism of Bile Acids Could Contribute to the Bariatric Surgery Improvements in Extreme Obesity. Metabolites. 2021 Oct 27;11(11):733. doi: 10.3390/metabo11110733.

  PMID: 34822391 BACKGROUND

• Gentile JKA, Oliveira KD, Pereira JG, Tanaka DY, Guidini GN, Cadona MZ, Siriani-Ribeiro DW, Perondini MT. THE INTESTINAL MICROBIOME IN PATIENTS UNDERGOING BARIATRIC SURGERY: A SYSTEMATIC REVIEW. Arq Bras Cir Dig. 2022 Dec 19;35:e1707. doi: 10.1590/0102-672020220002e1707. eCollection 2022.

  PMID: 36542005 BACKGROUND

• Thakur U, Bhansali A, Gupta R, Rastogi A. Liraglutide Augments Weight Loss After Laparoscopic Sleeve Gastrectomy: a Randomised, Double-Blind, Placebo-Control Study. Obes Surg. 2021 Jan;31(1):84-92. doi: 10.1007/s11695-020-04850-4. Epub 2020 Jul 12.

  PMID: 32656729 BACKGROUND

• Chaar ME, Lundberg P, Stoltzfus J. Thirty-day outcomes of sleeve gastrectomy versus Roux-en-Y gastric bypass: first report based on Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. Surg Obes Relat Dis. 2018 May;14(5):545-551. doi: 10.1016/j.soard.2018.01.011. Epub 2018 Jan 13.

  PMID: 29551470 BACKGROUND

• Lewis CA, de Jersey S, Seymour M, Hopkins G, Hickman I, Osland E. Iron, Vitamin B12, Folate and Copper Deficiency After Bariatric Surgery and the Impact on Anaemia: a Systematic Review. Obes Surg. 2020 Nov;30(11):4542-4591. doi: 10.1007/s11695-020-04872-y. Epub 2020 Aug 12.

  PMID: 32785814 BACKGROUND

• James H, Lorentz P, Collazo-Clavell ML. Patient-Reported Adherence to Empiric Vitamin/Mineral Supplementation and Related Nutrient Deficiencies After Roux-en-Y Gastric Bypass. Obes Surg. 2016 Nov;26(11):2661-2666. doi: 10.1007/s11695-016-2155-7.

  PMID: 27038046 BACKGROUND

• Meyer Mikalsen S, Aaseth J, Flaten TP, Whist JE, Bjorke-Monsen AL. Essential trace elements in Norwegian obese patients before and 12 months after Roux-en-Y gastric bypass surgery: Copper, manganese, selenium and zinc. J Trace Elem Med Biol. 2020 Dec;62:126650. doi: 10.1016/j.jtemb.2020.126650. Epub 2020 Sep 21.

  PMID: 33011630 BACKGROUND

• Arias PM, Domeniconi EA, Garcia M, Esquivel CM, Martinez Lascano F, Foscarini JM. Micronutrient Deficiencies After Roux-en-Y Gastric Bypass: Long-Term Results. Obes Surg. 2020 Jan;30(1):169-173. doi: 10.1007/s11695-019-04167-x.

  PMID: 31502183 BACKGROUND

Related Links

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MeSH Terms

Conditions

Obesity, Morbid; Metabolic Syndrome; Diabetes Mellitus; Hypertension; Sleep Apnea, Obstructive

Interventions

Glucagon-Like Peptide-1 Receptor Agonists

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Andrew Wheeler, MD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Randolph

CONTACT

573-882-4387; muresearchirb@missouri.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Model Details: Patients will be continued on currently prescribed GLP-1 agonist after bariatric surgery or medication will be held

Study Record Dates

• First Submitted: November 2, 2023
• First Posted: November 15, 2023
• Study Start: February 1, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2030
• Last Updated: January 22, 2026

Record last verified: 2025-07

Locations

US (1)