Use of Glucagon-like peptide 2 (GLP-2) analogs in inflammatory bowel disease
DOI:
https://doi.org/10.12775/QS.2024.17.53227Keywords
GLP-2, inflammatory bowel disease, Crohn's disease, ulcerative colitis, short bowel syndromeAbstract
Introduction:
Inflammatory bowel disease (IBD) is a chronic condition that involves long-term treatment and chronic idiopathic inflammation within the gastrointestinal tract. The predominant forms of IBD are: Crohn's disease and ulcerative colitis. These diseases cause significant physical as well as psychological dysfunction - patients with this condition are thought to have an increased risk of depression as well as anxiety. Standard treatment for IBD most commonly includes aminosalicylates, corticosteroids, immunomodulatory drugs, and biologic therapy. In some cases, particularly when it comes to Crohn's disease, it is necessary to remove a portion of the inflamed bowel. Multiple segmental bowel resections can result in the rare but serious complication of short bowel syndrome, which leads to intestinal failure and necessitates parenteral nutrition.
Glucagon-like peptide-2 exhibits intestinotropic properties and also acts as a growth factor in the gastrointestinal tract, thereby increasing intestinal perfusion, causing increased absorption of nutrients, and enhancing proliferative mechanisms while inhibiting apoptotic processes.
Methods:
We carefully reviewed the medical literature on inflammatory bowel disease, short bowel syndrome and the potential treatment of this condition with GLP-2 and its analogs. The materials for the analysis we presented came from the PubMed database.
Conclusions:
Glucagon-like peptide 2 (GLP-2) analogs may prove to be new treatments for short bowel syndrome (SBS). They exhibit growth-stimulating effects on the intestinal membrane and promote normal function.
References
Zatorski H, Sałaga M, Fichna J. Role of glucagon-like peptides in inflammatory bowel diseases—current knowledge and future perspectives. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2019;392(11):1321-1330. doi:https://doi.org/10.1007/s00210-019-01698-z
Yusta B, Matthews D, Flock GB, et al. Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway. Molecular Metabolism. 2017;6(6):503-511. doi:https://doi.org/10.1016/j.molmet.2017.03.006
Borghini R, Caronna R, Donato G, Picarelli A. GLP-2 analog Teduglutide in active Crohn’s disease and short bowel syndrome: Confirmation of anti-inflammatory role and future perspectives. Digestive and Liver Disease. 2020;52(6):686-687. doi:https://doi.org/10.1016/j.dld.2020.03.019
Gu J, Liu J, Huang T, et al. The protective and anti-inflammatory effects of a modified glucagon-like peptide-2 dimer in inflammatory bowel disease. Biochemical Pharmacology. 2018;155:425-433. doi:https://doi.org/10.1016/j.bcp.2018.07.027
Bisgaard TH, Allin KH, Keefer L, Ananthakrishnan AN, Jess T. Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment. Nature Reviews Gastroenterology & Hepatology. Published online June 22, 2022. doi:https://doi.org/10.1038/s41575-022-00634-6
Cai Z, Wang S, Li J. Treatment of Inflammatory Bowel Disease: a Comprehensive Review. Frontiers in Medicine. 2021;8(765474). doi:https://doi.org/10.3389/fmed.2021.765474
Sigalet DL. Advances in glucagon like peptide-2 therapy. physiology, current indications and future directions. Seminars in Pediatric Surgery. 2018;27(4):237-241. doi:https://doi.org/10.1053/j.sempedsurg.2018.07.008
Drucker DJ, Yusta B. Physiology and Pharmacology of the Enteroendocrine Hormone Glucagon-Like Peptide-2. Annual Review of Physiology. 2014;76(1):561-583. doi:https://doi.org/10.1146/annurev-physiol-021113-170317
Agersnap MA, Sonne K, Knudsen KM, Knudsen CB, Berner-Hansen M. Pharmacokinetics of Glepaglutide, A Long-Acting Glucagon-Like Peptide-2 Analogue: A Study in Healthy Subjects. Clinical Drug Investigation. 2022;42(12):1093-1100. doi:https://doi.org/10.1007/s40261-022-01210-1
Naimi RM, Hvistendahl MK, Poulsen SS, et al. Effects of glepaglutide, a long‐acting glucagon‐like peptide‐2 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial. JPEN, Journal of parenteral and enteral nutrition/JPEN Journal of parenteral and enteral nutrition. 2022;47(1):140-150. doi:https://doi.org/10.1002/jpen.2389
Kounatidis D, Vallianou NG, Tsilingiris D, et al. Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives. Current Nutrition Reports. 2022;11(4):618-642. doi:https://doi.org/10.1007/s13668-022-00433-0
Agersnap MA, Sonne K, Knudsen KM, Sulowicz W. Pharmacokinetics, Safety, and Tolerability of Glepaglutide, a Long-Acting GLP-2 Analog, in Subjects with Renal Impairment. Clinical Pharmacokinetics. Published online February 21, 2023. doi:https://doi.org/10.1007/s40262-023-01215-9
Zhu C, Li Y. An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults. The Journal of International Medical Research. 2022;50(3):3000605221086145. doi:https://doi.org/10.1177/03000605221086145
Massironi S, Cavalcoli F, Rausa E, Invernizzi P, Braga M, Vecchi M. Understanding short bowel syndrome: Current status and future perspectives. Digestive and Liver Disease. 2019;52(3). doi:https://doi.org/10.1016/j.dld.2019.11.013
Pironi L. Definition, classification, and causes of short bowel syndrome. Nutrition in Clinical Practice. 2023;38(S1). doi:https://doi.org/10.1002/ncp.10955
López Romero-Salazar F, Martínez Montiel P, Lal S. Chronic intestinal failure: an overview and future perspectives. Revista Española de Enfermedades Digestivas. Published online 2022. doi:https://doi.org/10.17235/reed.2022.8827/2022
Pironi L. Definitions of intestinal failure and the short bowel syndrome. Best Practice & Research Clinical Gastroenterology. 2016;30(2):173-185. doi:https://doi.org/10.1016/j.bpg.2016.02.011
Bering J, DiBaise JK. Short bowel syndrome: Complications and management. Nutrition in Clinical Practice. 2023;38(S1). doi:https://doi.org/10.1002/ncp.10978
Marcin Rudziński, Michał Ławiński, Gradowski Ł, et al. Kidney stones are common in patients with short‐bowel syndrome receiving long‐term parenteral nutrition: A predictive model for urolithiasis. JPEN, Journal of parenteral and enteral nutrition/JPEN Journal of parenteral and enteral nutrition. 2021;46(3):671-677. doi:https://doi.org/10.1002/jpen.2133
Nygaard L, Skallerup A, Olesen SS, et al. Osteoporosis in patients with intestinal insufficiency and intestinal failure: Prevalence and clinical risk factors. Clinical Nutrition. 2018;37(5):1654-1660. doi:https://doi.org/10.1016/j.clnu.2017.07.018
Gao X, Zhang L, Wang S, et al. Prevalence, Risk Factors, and Complications of Cholelithiasis in Adults With Short Bowel Syndrome: A Longitudinal Cohort Study. Frontiers in Nutrition. 2021;8. doi:https://doi.org/10.3389/fnut.2021.762240
Pironi L, Arends J, Bozzetti F, et al. ESPEN guidelines on chronic intestinal failure in adults. Clinical Nutrition. 2016;35(2):247-307. doi:https://doi.org/10.1016/j.clnu.2016.01.020
Pironi L, Allard JP, Joly F, Parnia Geransar, Genestin E, Pape U. Use of teduglutide in adults with short bowel syndrome–associated intestinal failure. Nutrition in Clinical Practice. Published online June 9, 2023. doi:https://doi.org/10.1002/ncp.11015
Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide Reduces Need for Parenteral Support Among Patients With Short Bowel Syndrome With Intestinal Failure. Gastroenterology. 2012;143(6):1473-1481.e3. doi:https://doi.org/10.1053/j.gastro.2012.09.007
Gigola F, Maria Chiara Cianci, Cirocchi R, et al. Use of Teduglutide in Children With Intestinal Failure: A Systematic Review. Frontiers in nutrition. 2022;9. doi:https://doi.org/10.3389/fnut.2022.866518
Roda G, Chien Ng S, Kotze PG, et al. Crohn’s disease. Nature Reviews Disease Primers. 2020;6(1):1-19. doi:https://doi.org/10.1038/s41572-020-0156-2
Petagna L, Antonelli A, Ganini C, et al. Pathophysiology of Crohn’s disease inflammation and recurrence. Biology Direct. 2020;15(1). doi:https://doi.org/10.1186/s13062-020-00280-5
Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s Disease. The Lancet. 2017;389(10080):1741-1755. doi:https://doi.org/10.1016/s0140-6736(16)31711-1
Mitchel EB, Rosh JR. Pediatric Management of Crohn’s Disease. Gastroenterology Clinics of North America. 2022;51(2):401-424. doi:https://doi.org/10.1016/j.gtc.2021.12.013
Cushing K, Higgins PDR. Management of Crohn Disease. JAMA. 2021;325(1):69. doi:https://doi.org/10.1001/jama.2020.18936
Gajendran M, Loganathan P, Catinella AP, Hashash JG. A comprehensive review and update on Crohn’s disease. Disease-a-month: DM. 2018;64(2):20-57. doi:https://doi.org/10.1016/j.disamonth.2017.07.001
Danese S, Fiorino G, Mary JY, et al. Development of Red Flags Index for Early Referral of Adults with Symptoms and Signs Suggestive of Crohn’s Disease: An IOIBD Initiative. Journal of Crohn’s and Colitis. 2015;9(8):601-606. doi:https://doi.org/10.1093/ecco-jcc/jjv067
Catherine Le Berre, Sailish Honap, Laurent Peyrin-Biroulet. Ulcerative colitis. The Lancet. 2023;402(10401):571-584. doi:https://doi.org/10.1016/s0140-6736(23)00966-2
Du L, Ha C. Epidemiology and Pathogenesis of Ulcerative Colitis. Gastroenterology Clinics of North America. 2020;49(4):643-654. doi:https://doi.org/10.1016/j.gtc.2020.07.005
Porter RJ, Kalla R, Ho GT. Ulcerative colitis: Recent advances in the understanding of disease pathogenesis. F1000Research. 2020;9. doi:https://doi.org/10.12688/f1000research.20805.1
Kucharzik T, Koletzko S, Kannengießer K, Dignaß A. Ulcerative Colitis—Diagnostic and Therapeutic Algorithms. Deutsches Aerzteblatt Online. 2020;117(33-34):564-574. doi:https://doi.org/10.3238/arztebl.2020.0564
Feuerstein JD, Moss AC, Farraye FA. Ulcerative Colitis. Mayo Clinic Proceedings. 2019;94(7):1357-1373. doi:https://doi.org/10.1016/j.mayocp.2019.01.018
Kobayashi T, Siegmund B, Le Berre C, et al. Ulcerative colitis. Nature Reviews Disease Primers. 2020;6(1):74. doi:https://doi.org/10.1038/s41572-020-0205-x
Janssen J, Rotondo A, Mulè F, Tack J. Review article: a comparison of glucagon-like peptides 1 and 2. 2012;37(1):18-36. doi:https://doi.org/10.1111/apt.12092
Pietro Lucotti, Elisabetta Lovati, Marco Vincenzo Lenti, et al. Abnormal post-prandial glucagon-like peptide release in patients with Crohn’s disease. Clinics and research in hepatology and gastroenterology. 2021;45(4):101533-101533. doi:https://doi.org/10.1016/j.clinre.2020.08.011
Buchman AL, Katz S, Fang JC, Bernstein CN, Abou-Assi SG. Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohnʼs disease. 2010;16(6):962-973. doi:https://doi.org/10.1002/ibd.21117
Kochar B, Long MD, Shelton E, et al. Safety and Efficacy of Teduglutide (Gattex) in Patients With Crohn’s Disease and Need for Parenteral Support Due to Short Bowel Syndrome–associated Intestinal Failure. Journal of Clinical Gastroenterology. 2017;51(6):508-511. doi:https://doi.org/10.1097/mcg.0000000000000604
Alters SE, McLaughlin B, Spink B, et al. GLP2-2G-XTEN: A Pharmaceutical Protein with Improved Serum Half-Life and Efficacy in a Rat Crohn’s Disease Model. Mukhopadhyay P, ed. PLoS ONE. 2012;7(11):e50630. doi:https://doi.org/10.1371/journal.pone.0050630
Li D, Yang Y, Yin X, et al. Glucagon-like peptide (GLP) -2 improved colonizing bacteria and reduced severity of ulcerative colitis by enhancing the diversity and abundance of intestinal mucosa. Bioengineered. 2021;12(1):5195-5209. doi:https://doi.org/10.1080/21655979.2021.1958600
Li D, Gao Y, Cui L, et al. Integrative analysis revealed the role of glucagon-like peptide-2 in improving experimental colitis in mice by inhibiting inflammatory pathways, regulating glucose metabolism, and modulating gut microbiota. Frontiers in microbiology. 2023;14. doi:https://doi.org/10.3389/fmicb.2023.1174308
Fifi A, Raphael BP, Terreri B, Uddin S, Kaufman SS. Effects of Teduglutide on Diarrhea in Pediatric Patients with Short Bowel Syndrome-Associated Intestinal Failure. Journal of pediatric gastroenterology and nutrition. 2023;77(5):666-671. doi:https://doi.org/10.1097/mpg.0000000000003922
Dong Wook Kim, Kim E, Bertram K, Daniel Sungku Rim, Nolen-Doerr E, Shin JH. Long-term outcomes and adverse effects of teduglutide in patients with short bowel syndrome: Highlighting hyperamylasemia and hyperlipasemia. American journal of health-system pharmacy. 2023;81(4):146-152. doi:https://doi.org/10.1093/ajhp/zxad274
Rosete BE, Wendel D, Horslen SP. Teduglutide for pediatric short bowel syndrome patients. Expert Review of Gastroenterology & Hepatology. 2021;15(7):727-733. doi:https://doi.org/10.1080/17474124.2021.1913052
Kocoshis SA, Merritt RJ, Hill S, et al. Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24‐Week, Phase III Study. Journal of Parenteral and Enteral Nutrition. 2019;44(4):621-631. doi:https://doi.org/10.1002/jpen.1690
Hansen NL, Brønden A, Nexøe-Larsen CC, et al. Glucagon-Like Peptide 2 Inhibits Postprandial Gallbladder Emptying in Man: A Randomized, Double-Blinded, Crossover Study. Clinical and Translational Gastroenterology. 2020;11(12):e00257. doi:https://doi.org/10.14309/ctg.0000000000000257
Pironi L, Raschi E, Sasdelli AS. The safety of available treatment options for short bowel syndrome and unmet needs. Expert Opinion on Drug Safety. 2021;20(12):1501-1513. doi:https://doi.org/10.1080/14740338.2021.1940947
Pizzoferrato M, Puca P, Ennas S, Cammarota G, Guidi L. Glucagon-like peptide-2 analogues for Crohn’s disease patients with short bowel syndrome and intestinal failure. World journal of gastroenterology. 2022;28(44):6258-6270. doi:https://doi.org/10.3748/wjg.v28.i44.6258
Jeppesen PB, Gabe SM, Seidner DL, Lee HM, Olivier C. Factors Associated With Response to Teduglutide in Patients With Short-Bowel Syndrome and Intestinal Failure. Gastroenterology. 2018;154(4):874-885. doi:https://doi.org/10.1053/j.gastro.2017.11.023
Mayo BJ, Secombe KR, Wignall AD, et al. The GLP-2 analogue elsiglutide reduces diarrhoea caused by the tyrosine kinase inhibitor lapatinib in rats. Cancer chemotherapy and pharmacology. 2020;85(4):793-803. doi:https://doi.org/10.1007/s00280-020-04040-0
Reiner J, Berlin P, Held J, et al. Dapiglutide, a novel dual GLP‐1 and GLP‐2 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel. JPEN, Journal of parenteral and enteral nutrition/JPEN Journal of parenteral and enteral nutrition. 2021;46(5):1107-1118. doi:https://doi.org/10.1002/jpen.2286
Billiauws L, Maggiori L, Joly F, Panis Y. Medical and surgical management of short bowel syndrome. Journal of Visceral Surgery. 2018;155(4):283-291. doi:https://doi.org/10.1016/j.jviscsurg.2017.12.012
Reitzel RA, Rosenblatt J, Chaftari A, Raad II. Epidemiology of Infectious and Noninfectious Catheter Complications in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Meta‐Analysis. Journal of Parenteral and Enteral Nutrition. 2019;43(7):832-851. doi:https://doi.org/10.1002/jpen.1609
Pironi L, Sasdelli AS. Intestinal Failure-Associated Liver Disease. Clinics in Liver Disease. 2019;23(2):279-291. doi:https://doi.org/10.1016/j.cld.2018.12.009
Jeppesen PB. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut. 2005;54(9):1224-1231. doi:https://doi.org/10.1136/gut.2004.061440
S.E. Martchenko, Sweeney ME, V. Dimitriadou, Murray JA, Brubaker PL. Site-Specific and Temporal Effects of Apraglutide, a Novel Long-Acting Glucagon-Like Peptide-2 Receptor Agonist, on Intestinal Growth in Mice. The journal of pharmacology and experimental therapeutics/The Journal of pharmacology and experimental therapeutics. 2020;373(3):347-352. doi:https://doi.org/10.1124/jpet.119.263947
Eliasson J, Hvistendahl MK, Freund N, Bolognani F, Meyer C, Jeppesen PB. Apraglutide, a novel glucagon‐like peptide‐2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo‐controlled, randomized phase 2 trial. Journal of Parenteral and Enteral Nutrition. Published online September 7, 2021. doi:https://doi.org/10.1002/jpen.2223
Jolanta Skarbaliene, Jesper Mosolff Mathiesen, Bjarne Due Larsen, Thorkildsen C, Yvette Miata Petersen. Glepaglutide, a novel glucagon-like peptide-2 agonist, has anti-inflammatory and mucosal regenerative effects in an experimental model of inflammatory bowel disease in rats. BMC gastroenterology. 2023;23(1). doi:https://doi.org/10.1186/s12876-023-02716-4
Naimi RM, Hvistendahl M, Enevoldsen LH, et al. Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial. The Lancet Gastroenterology & Hepatology. 2019;4(5):354-363. doi:https://doi.org/10.1016/s2468-1253(19)30077-9
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