The Revolutionary Role of GLP-1 Agonists and SGLT-2 Inhibitors in Managing Diabetes and Chronic Kidney Disease in Liver Transplant Recipients
Main Article Content
Abstract
Successful liver transplant is the only life-saving intervention for patients with end-stage liver disease, but post-transplant complications, particularly diabetes mellitus and chronic kidney disease, significantly compromise both patient and graft survival. These complications not only heighten clinical and economic burdens but also worsen long-term outcomes due to the rising prevalence of metabolic syndrome, which predisposes many liver transplant recipients to metabolic dysfunctions like diabetes and chronic kidney disease. Additionally, metabolic syndrome is a key driver of Metabolic Associated Steatotic Liver Disease, a leading cause of liver failure and a growing indication for liver transplantation worldwide.
While liver transplantation resolves end stage liver disease, it fails to address the underlying metabolic challenges, such as pre-existing or post-transplant diabetes and chronic kidney disease. The use of calcineurin inhibitors ,a cornerstone of immunosuppression, exacerbates these issues by disrupting glucose metabolism, increasing insulin resistance, and causing pancreatic beta-cell dysfunction, which further contributes to post-transplant diabetes mellitus. Post-transplant diabetes mellitus is associated with increased morbidity, mortality, and graft rejection, underscoring the need for improved management strategies.
Emerging therapies, such as GLP-1 receptor agonists and SGLT-2 inhibitors, have shown promise in mitigating the effects of diabetes and chronic kidney disease in non-transplant populations. These agents offer potential benefits for liver transplant recipients by improving glycemic control, promoting weight loss, and offering renal protection. However, their application in liver transplantation remains underexplored, with limited clinical data available. This review explores the pathogenesis of diabetes and chronic kidney disease in liver transplant recipients, the challenges posed by current immunosuppressive regimens, and the potential role of GLP-1 agonists and SGLT-2 inhibitors in improving patient and graft outcomes. Future research is essential to optimize post-transplant care and reduce the burden of metabolic complications in liver transplant recipients.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. Yanai H, Adachi H, Hakoshima M, Iida S, Katsuyama H. Metabolic-dysfunction-associated steatotic liver disease—its pathophysiology, association with atherosclerosis and cardiovascular disease, and treatments. Int J Mol Sci. 2023;24 (20):15473. doi:10.3390/ijms242015473
3. United Network for Organ Sharing. Innovations and policy updates drive equity and a record number of lifesaving organ transplants in 2023. UNOS. Published January 11, 2024. https://unos.org/media-resources/releases/innovations-policy-updates-drive-equity-and-record-organ-transplants-2023/. Accessed October 3, 2024.
4. Younossi ZM, Stepanova M, Al Shabeeb R, et al. The changing epidemiology of adult liver transplantation in the United States in 2013-2022: the dominance of metabolic dysfunction–associated steatotic liver disease and alcohol-associated liver disease. Hepatology Commun. 2023;8(1). doi:10.1097/HC9.0000000000000352
5. Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: disease burden, current management and future challenges. JHEP Rep. 2020;2(6):100192. doi:10.1016/j.jhepr.2020.100192
6. Pham P, Sarkar M, Pham P, Pham P. Diabetes mellitus after solid organ transplantation. Endotext. Published July 13, 2022. https://www.ncbi.nlm.nih.gov/books/NBK378977/. Accessed October 3, 2024.
7. Martín-Timón I. Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J Diabetes. 2014;5(4):444-470. doi:10.4239/wjd.v5.i4.444
8. Shivaswamy V, Boerner B, Larsen J. Post-transplant diabetes mellitus: causes, treatment, and impact on outcomes. Endocr Rev. 2016;37(1) :37-61. doi:10.1210/er.2015-1084
9. Florencia Z, Christos M. Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr. 2009;91(1):258S-261S. doi:10.3945/ajcn.2009.28449C
10. Serna-Higuita LM, Isaza-López MC, Hernández-Herrera GN, et al. Development and validation of a new score to assess the risk of posttransplantation diabetes mellitus in kidney transplant recipients. Transplantation Direct. 2023; 9(12). doi:10.1097/txd.0000000000001558
11. Lindsay RS, Funahashi T, Hanson RL, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet. 2002;360 (9326):57-58. doi:10.1016/s0140-6736(02)09335-2
12. Cullaro G, Verna EC, Lee BP, Lai JC. Chronic kidney disease in liver transplant candidates: a rising burden impacting post–liver transplant outcomes. Liver Transpl. 2020;26(4):498-506. doi:10.1002/lt.25694
13. Ahmed SH, Biddle K, Augustine T, Azmi S. Post-transplantation diabetes mellitus. Diabetes Ther. 2020;11(4):779-801. doi:10.1007/s13300-020-00790-5
14. Poltronieri Pacheco M, Carneiro-D’Albuquerque LA, Ferraz D. Current aspects of renal dysfunction after liver transplantation. World J Hepatol. 2022;14(1):45-61. doi:10.4254/wjh.v14.i1.45
15. Robertson FP, Yeung AC, Male V, et al. Urinary neutrophil gelatinase associated lipocalins (NGALs) predict acute kidney injury post liver transplant. HPB (Oxford). 2019;21(4):473-481. doi:10.1016/j.hpb.2018.09.017
16. Meloni AR, DeYoung MB, Lowe C, Parkes DG. GLP-1 receptor activated insulin secretion from pancreatic β-cells: mechanism and glucose dependence. Diabetes Obes Metab. 2012;15(1): 15-27. doi:10.1111/j.1463-1326.2012.01663.x
17. Anderson JE. Combining glucagon-like peptide 1 receptor agonists and sodium–glucose cotransporter 2 inhibitors to target multiple organ defects in type 2 diabetes. Diabetes Spectr. Published April 3, 2020. doi:10.2337/ds19-0031
18. Yu JH, Park SY, Lee DY, Kim NH, Seo JA. GLP-1 receptor agonists in diabetic kidney disease: current evidence and future directions. Kidney Res Clin Pract. 2022;41(2):136-149. doi:10.23876/j.krcp.22.001
19. Richardson SH, Wong G, Garner E, Izzy M, Srivastava G. Utility of glucagon-like peptide 1 receptor agonists as anti-obesity medications in liver transplant recipients. Liver Transpl. 2024;30 (2):226-228. doi:10.1097/LVT.0000000000000233
20. Pham PTT, Pham PCT. Optimal use of SGLT2 inhibitors in diabetic kidney transplant recipients. Front Nephrol. 2022;2. doi:10.3389/fneph.2022.1014241
21. Padda IS, Mahtani AU, Parmar M. Sodium-glucose transport protein 2 (SGLT2) inhibitors. PubMed. Published 2022. https://www.ncbi.nlm.nih.gov/books/NBK576405/. Accessed October 3, 2024.
22. Berkovic MC, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol. 2020;26(21):2740-2757. doi:10.3748/wjg.v26.i21.2740
23. Zheng K, Azhie A, You X, et al. Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors for the treatment of diabetes mellitus in liver transplant recipients. Diabetes Obes Metab. 2024;26(10):4261-4272. doi:10.1111/dom.15769
24. Baar MJB van, Ruiten CC van, Muskiet MHA, Bloemendaal L van, IJzerman RG, Raalte DH van. SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management. Diabetes Care. 2018;41(8): 1543-1556. doi:https://doi.org/10.2337/dc18-0588