A Retrospective Analysis of Glucagon-Like Peptide 1 Receptor Agonists in Treating Type 2 Diabetes Mellitus Complicated by Nonalcoholic Fatty Liver Disease
Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P < 0.05). Aspartate aminotransferase (AST) and high-density lipoprotein cholesterol (HDL-C) levels did not change significantly compared to the levels before treatment (P > 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P < 0.05), as were the changes in L/S, TC, and TG in the ultra-long-acting group after treatment (P < 0.05). LDL-C levels after treatment with ultra-long-acting GLP-1RA showed a difference at the 0.05 significance level from LDL-C levels after treatment with long-acting GLP-1RA. No statistically significant differences were observed in the levels of L/S, ALT, AST, GGT, TC, TG, and HDL-C. Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.
References
[1]
Riazi, K., Azhari, H., Charette, J.H., Underwood, F.E., King, J.A., Afshar, E.E., et al. (2022) The Prevalence and Incidence of Nafld Worldwide: A Systematic Review and Meta-Analysis. The Lancet Gastroenterology & Hepatology, 7, 851-861. https://doi.org/10.1016/S2468-1253(22)00165-0
[2]
Mantovani, A., Petracca, G., Beatrice, G., Csermely, A., Lonardo, A. and Targher, G. (2021) Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Metabolites, 11, No. 73. https://doi.org/10.3390/metabo11020073
[3]
Majumdar, A., Verbeek, J. and Tsochatzis, E.A. (2021) Non-Alcoholic Fatty Liver Disease: Current Therapeutic Options. Current Opinion in Pharmacology, 61, 98-105. https://doi.org/10.1016/j.coph.2021.09.007
[4]
Raza, S., Rajak, S., Upadhyay, A., Tewari, A. and Anthony Sinha, R. (2021) Current Treatment Paradigms and Emerging Therapies for Nafld/Nash. Frontiers in Bioscience, 26, 206-237. https://doi.org/10.2741/4892
[5]
Gupta, N.A., Mells, J., Dunham, R.M., Grakoui, A., Handy, J., Saxena, N.K., et al. (2010) Glucagon-Like Peptide-1 Receptor Is Present on Human Hepatocytes and Has a Direct Role in Decreasing Hepatic Steatosis in Vitro by Modulating Elements of the Insulin Signaling Pathway. Hepatology, 51, 1584-1592. https://doi.org/10.1002/hep.23569
[6]
Newsome, P.N., Buchholtz, K., Cusi, K., Linder, M., Okanoue, T., Ratziu, V., et al. (2021) A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. The New England Journal of Medicine, 384, 1113-1124. https://doi.org/10.1056/NEJMoa2028395
[7]
Armstrong, M.J., Gaunt, P., Aithal, G.P., Barton, D., Hull, D., Parker, R., et al. (2016) Liraglutide Safety and Efficacy in Patients with Non-Alcoholic Steatohepatitis (Lean): A Multicentre, Double-Blind, Randomised, Placebo-Controlled Phase 2 Study. The Lancet, 387, 679-690. https://doi.org/10.1016/S0140-6736(15)00803-X
[8]
Pafili, K. and Roden, M. (2021) Nonalcoholic Fatty Liver Disease (Nafld) from Pathogenesis to Treatment Concepts in Humans. Molecular Metabolism, 50, No. 101122. https://doi.org/10.1016/j.molmet.2020.101122
[9]
Buzzetti, E., Pinzani, M. and Tsochatzis, E.A. (2016) The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (Nafld). Metabolism: Clinical and Experimental, 65, 1038-1048. https://doi.org/10.1016/j.metabol.2015.12.012
[10]
Vogel, A., Meyer, T., Sapisochin, G., Salem, R. and Saborowski, A. (2022) Hepatocellular Carcinoma. The Lancet, 400, 1345-1362. https://doi.org/10.1016/S0140-6736(22)01200-4
[11]
Nauck, M.A., Quast, D.R., Wefers, J. and Pfeiffer, A.F.H. (2021) The Evolving Story of Incretins (Gip and Glp-1) in Metabolic and Cardiovascular Disease: A Pathophysiological Update. Diabetes, Obesity & Metabolism, 23 Suppl 3, 5-29. https://doi.org/10.1111/dom.14496
[12]
Petrovic, A., Igrec, D., Rozac, K., Bojanic, K., Kuna, L., Kolaric, T.O., et al. (2023) The Role of Glp1-Ras in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using in Vitro Models of Nafld. Current Issues in Molecular Biology, 45, 4544-4556. https://doi.org/10.3390/cimb45060288
[13]
Khoo, J., Hsiang, J.C., Taneja, R., Koo, S.H., Soon, G.H., Kam, C.J., et al. (2019) Randomized Trial Comparing Effects of Weight Loss by Liraglutide with Lifestyle Modification in Non-Alcoholic Fatty Liver Disease. Liver International: Official Journal of the International Association for the Study of the Liver, 39, 941-949. https://doi.org/10.1111/liv.14065
[14]
Tan, Y., Zhen, Q., Ding, X., Shen, T., Liu, F., Wang, Y., et al. (2022) Association between Use of Liraglutide and Liver Fibrosis in Patients with Type 2 Diabetes. Frontiers in Endocrinology, 13, 935180. https://doi.org/10.3389/fendo.2022.935180
[15]
Xu, D., Nair, A., Sigston, C., Ho, C., Li, J., Yang, D., et al. (2022) Potential Roles of Glucagon-Like Peptide 1 Receptor Agonists (Glp-1 Ras) in Nondiabetic Populations. Cardiovascular Therapeutics, 2022, No. 6820377. https://doi.org/10.1155/2022/6820377
[16]
Feng, W.H., Bi, Y., Li, P., Yin, T.T., Gao, C.X., Shen, S.M., et al. (2019) Effects of Liraglutide, Metformin and Gliclazide on Body Composition in Patients with Both Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Randomized Trial. Journal of Diabetes investigation, 10, 399-407. https://doi.org/10.1111/jdi.12888
[17]
Loomba, R., Abdelmalek, M.F., Armstrong, M.J., Jara, M., Kjaer, M.S., Krarup, N., et al. (2023) Semaglutide 2·4 Mg Once Weekly in Patients with Non-Alcoholic Steatohepatitis-Related Cirrhosis: A Randomised, Placebo-Controlled Phase 2 Trial. The Lancet Gastroenterology & Hepatology, 8, 511-522. https://doi.org/10.1016/S2468-1253(23)00068-7
[18]
Yuan, X., Gao, Z., Hao, Z., Ma, H., Duan, K. and Yang, C. (2023) Effect of Long-Acting Versus Short-Acting Glucagon-Like Peptide-1 Receptor Agonists on Improving Body Weight and Related Metabolic Parameters in Type 2 Diabetes: A Head-to-Head Meta-Analysis. Medicine, 102, No. e35739. https://doi.org/10.1097/MD.0000000000035739