Glucagon-like-peptide 1 (GLP-1) Receptor Agonists in Rheumatologic Disease

Jill Trinacty; Krista Rostom

doi:10.58931/crt.2025.2158

Authors

Jill Trinacty, MD LMC Ottawa, Bariatric Medical Institute, Queensway Carleton Hospital, Bruyère Continuing Care, University of Ottawa
Krista Rostom, MD West Ottawa Specialty Care, Queensway Carleton Hospital

DOI:

https://doi.org/10.58931/crt.2025.2158

Abstract

Obesity is a complex chronic disease that increases the risk of long-term medical complications and reduces lifespan due to excess body fat or adiposopathy. As of 2016, obesity affects 8.3 million (26.4%) of the Canadian population. Severe obesity, defined as a body mass index (BMI) >35 kg/m², affects an estimated 1.9 million Canadians. The financial burden of obesity, including both direct and indirect costs, was estimated to be $7.1 billion in 2010. The pathophysiology of obesity is complex and involves a combination of genetic, metabolic, behavioural, and environmental factors. The hypothalamus regulates appetite and energy expenditure, while the mesolimbic area controls the emotional, pleasurable, and rewarding aspects of eating. The cognitive lobe is responsible for overriding the hedonic drive of the mesolimbic system. Adipose tissue itself contributes to its regulation through the release of leptin in proportion to fat mass. Leptin binds to receptors in the hypothalamus to reduce appetite and increase energy expenditure. Similarly, insulin binds to receptors in the arcuate nucleus of the hypothalamus also reducing appetite and increasing energy expenditure.

Author Biographies

Jill Trinacty, MD, LMC Ottawa, Bariatric Medical Institute, Queensway Carleton Hospital, Bruyère Continuing Care, University of Ottawa

Dr. Trinacty is originally from Nova Scotia, where she obtained her Bachelor of Science (Honours) degree at Saint Francis Xavier University in Antigonish. She completed her medical degree at Dalhousie University. Dr. Trinacty completed residency in Internal Medicine and specialization in Endocrinology and Metabolism at The Ottawa Hospital. She is a diplomate of the American Board of Obesity Medicine. She practices at LMC Ottawa, Queensway Carleton Hospital, and Bariatric Medical Institute. She is a consultant and affiliate researcher with Bruyere Continuing Care. She is presently a lecturer at the University of Ottawa. She also serves as Vice Chair of the Endocrinology Section for the OMA and is an editor of the journal Canadian Diabetes and Endocrinology Today.

Krista Rostom, MD, West Ottawa Specialty Care, Queensway Carleton Hospital

Dr. Rostom obtained her Bachelor of Science in Engineering at Queen’s University and her medical degree at Dalhousie University. Dr. Rostom completed her residency in Internal Medicine and her Rheumatology fellowship at The University of Ottawa and The Ottawa Hospital. She is a community Rheumatologist practicing in her general rheumatology outpatient clinic as well as seeing patients in hospital as a consultant.

References

Wharton S, Lau DC, Vallis M, Sharma AM, Biertho L, Campbell-Scherer D, et al. Obesity in adults: a clinical practice guideline. CMAJ. 2020;192(31):E875-E891. doi:10.1503/cmaj.191707 DOI: https://doi.org/10.1503/cmaj.191707

Guimarães MF, Rodrigues CE, Gomes KW, Machado CJ, Brenol CV, Krampe SF, et al. High prevalence of obesity in rheumatoid arthritis patients: association with disease activity, hypertension, dyslipidemia and diabetes, a multi-center study. Adv Rheumatol. 2019;59(1):44. doi:10.1186/s42358-019-0089-1 DOI: https://doi.org/10.1186/s42358-019-0089-1

Dar L, Tiosano S, Watad A, Bragazzi NL, Zisman D, Comaneshter D, et al. Are obesity and rheumatoid arthritis interrelated Int J Clin Pract. 2018;72(1): 10.1111/ijcp.13045. doi:10.1111/ijcp.13045 DOI: https://doi.org/10.1111/ijcp.13045

Maas F, Arends S, van der Veer E, Wink F, Efde M, Bootsma H, et al. Obesity is common in axial spondyloarthritis and is associated with poor clinical outcome. J Rheumatol. 2016;43(2):383-387. doi:10.3899/jrheum.150648

Drucker DJ. Efficacy and safety of GLP-1 medicines for type 2 diabetes and obesity. Diabetes Care. 2024 Nov 1;47(11):1873-1888. doi:10.2337/dci24-0003 DOI: https://doi.org/10.2337/dci24-0003

Zheng Z, Zong Y, Ma Y, Tian Y, Pang Y, Zhang C, et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduct Target Ther. 2024;9(1):234. doi:10.1038/s41392-024-01931-z DOI: https://doi.org/10.1038/s41392-024-01931-z

Williams JC, Hum RM, Rogers K, Maglio C, Alam U, Zhao SS. Metabolic syndrome and psoriatic arthritis: the role of weight loss as a disease-modifying therapy. Ther Adv Musculoskelet Dis. 2024;16:1759720X241271886. doi:10.1177/1759720X241271886 DOI: https://doi.org/10.1177/1759720X241271886

Dubovyk V, Vasileiadis GK, Fatima T, Zhang Y, Kapetanovic MC, Kastbom A, et al. Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study. RMD Open. 2024;10(2):e004227. doi:10.1136/rmdopen-2024-004227 DOI: https://doi.org/10.1136/rmdopen-2024-004227

Levitsky A, Brismar K, Hafström I, Hambardzumyan K, Lourdudoss C, van Vollenhoven RF, et al. Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial. RMD Open. 2017;3(2):e000458. doi:10.1136/rmdopen-2017-000458 DOI: https://doi.org/10.1136/rmdopen-2017-000458

Liu Y, Hazlewood GS, Kaplan GG, Eksteen B, Barnabe C. Impact of obesity on remission and disease activity in rheumatoid arthritis: a systematic review and meta‐analysis. Arthritis Care Res (Hoboken). 2017;69(2):157-165. doi:10.1002/acr.22932 DOI: https://doi.org/10.1002/acr.22932

Abuhelwa AY, Hopkins AM, Sorich MJ, Proudman S, Foster DJ, Wiese MD. Association between obesity and remission in rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs. Sci Rep. 2020;10(1):18634. doi:10.1038/s41598-020-75673-7 DOI: https://doi.org/10.1038/s41598-020-75673-7

Kumthekar A, Ogdie A. Obesity and psoriatic arthritis: a narrative review. Rheumatol Ther. 2020;7(3):447-456. doi:10.1007/s40744-020-00215-6 DOI: https://doi.org/10.1007/s40744-020-00215-6

Leung YY, Eder L, Orbai AM, Coates LC, De Wit M, Smolen JS, et al. Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: a cross-sectional study. RMD Open. 2023;9(3):e003157. doi:10.1136/rmdopen-2023-003157 DOI: https://doi.org/10.1136/rmdopen-2023-003157

Maas F, Arends S, van der Veer E, Wink F, Efde M, Bootsma H, et al. Obesity is common in axial spondyloarthritis and is associated with poor clinical outcome. J Rheumatol. 2016;43(2):383-387. doi:10.3899/jrheum.150648 DOI: https://doi.org/10.3899/jrheum.150648

Ranganath VK, La Cava A, Vangala S, Brook J, Kermani TA, Furst DE, et al. Improved outcomes in rheumatoid arthritis with obesity after a weight loss intervention: randomized trial. Rheumatology (Oxford). 2023;62(2):565-574. doi:10.1093/rheumatology/keac307 DOI: https://doi.org/10.1093/rheumatology/keac307

Kreps DJ, Halperin F, Desai SP, Zhang ZZ, Losina E, Olson AT, et al. Association of weight loss with improved disease activity in patients with rheumatoid arthritis: a retrospective analysis using electronic medical record data Int J Clin Rheumtol. 2018;13(1):1-10. doi:10.4172/1758-4272.1000154 DOI: https://doi.org/10.4172/1758-4272.1000154

Klingberg E, Bilberg A, Björkman S, Hedberg M, Jacobsson L, Forsblad-d’Elia H, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21 (1):17. doi:10.1186/s13075-019-1810-5 DOI: https://doi.org/10.1186/s13075-019-1810-5

Karacabeyli D, Lacaille D. Glucagon-like peptide 1 receptor agonists in patients with inflammatory arthritis or psoriasis: a scoping review J Clin Rheumatol. 2024;30(1):26-31. doi:10.1097/RHU.0000000000001949 DOI: https://doi.org/10.1097/RHU.0000000000001949

Huffman KF, Ambrose KR, Nelson AE, Allen KD, Golightly YM, Callahan LF. The critical role of physical activity and weight management in knee and hip osteoarthritis: a narrative review. J Rheumatol. 2024;51(3):224-233. doi:10.3899/jrheum.2023-0819 DOI: https://doi.org/10.3899/jrheum.2023-0819

Bliddal H, Bays H, Czernichow S, Uddén Hemmingsson J, Hjelmesæth J, Hoffmann Morville T, et al. Once-weekly semaglutide in persons with obesity and knee osteoarthritis. N Engl J Med. 2024;391(17):1573-1583. doi:10.1056/NEJMoa2403664 DOI: https://doi.org/10.1056/NEJMoa2403664

Dente E, Kellner D, Tran V, Welsh T, Tran V, Saha A, et al. Effects of anti-obesity medications in RA patients. [abstract]. Arthritis Rheumatol. 2024;76 (suppl 9). https://acrabstracts.org/abstract/effects-of-anti-obesity-medications-in-ra-patients. Accessed April 28, 2025.

Sullivan C, Gaoatswe G, Gibney J, Healy ML, Doran M, Kane D, et al. Treatment with the glucagon-like peptide-1 analogue liraglutide is associated with amelioration of disease activity in a prospective cohort study of patients with inflammatory arthritis. [abstract]. Arthritis Rheumatol 2013;65:S630-S631. Accessed April 28, 2025

Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol. 2008;26(5 Suppl 51):S35-S61.

Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012;71(9):1524-1529. doi:10.1136/annrheumdis-2011-200726 DOI: https://doi.org/10.1136/annrheumdis-2011-200726

Aviña‐Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta‐analysis of observational studies. Arthritis Rheum. 2008;59(12):1690-1697. doi:10.1002/art.24092 DOI: https://doi.org/10.1002/art.24092

England BR, Thiele GM, Anderson DR, Mikuls TR. Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. BMJ. 2018;361:k1036. doi:10.1136/bmj.k1036 DOI: https://doi.org/10.1136/bmj.k1036

Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med . 2016;375(19):1834-1844. doi:10.1056/NEJMoa1607141 DOI: https://doi.org/10.1056/NEJMoa1607141

Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. doi:10.1016/S0140-6736(19)31149-3 DOI: https://doi.org/10.1016/S0140-6736(19)31149-3

Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563 DOI: https://doi.org/10.1056/NEJMoa2307563

Karacabeyli D, Lacaille D, Lu N, McCormick N, Xie H, Choi HK, Aviña-Zubieta JA. Mortality and major adverse cardiovascular events after glucagon-like peptide-1 receptor agonist initiation in patients with immune-mediated inflammatory diseases and type 2 diabetes: A population-based study. Plos one. 2024 Aug 8;19(8):e0308533. DOI: https://doi.org/10.1371/journal.pone.0308533

Glucagon-like-peptide 1 (GLP-1) Receptor Agonists in Rheumatologic Disease

Authors

DOI:

Abstract

Author Biographies

Jill Trinacty, MD, LMC Ottawa, Bariatric Medical Institute, Queensway Carleton Hospital, Bruyère Continuing Care, University of Ottawa

Krista Rostom, MD, West Ottawa Specialty Care, Queensway Carleton Hospital

References

Downloads

Published

How to Cite

Issue

Section

License

Summary

Open Access

Licence