Evolving Role of Semaglutide in NAFLD: in Combination, Weekly and Oral Administration

Overview

Journal Front Pharmacol

Date 2024 Mar 11

PMID 38464718

Authors

Evgenia Koureta

Evangelos Cholongitas

Affiliations

Soon will be listed here.

Abstract

Non alcoholic fatty disease (NAFLD) is the most common chronic liver disease that is managed in the liver departments. It seems that the prevalence of the disease is rising worldwide and as it has the same pathogenetic pathways with metabolic syndrome, treatments that target components of the metabolic syndrome seem promising for the therapy of NAFLD as well. In this review we discuss the evolving role of semaglutide, which is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that has been already approved for the treatment of type II diabetes mellitus (T2DM) and obesity.

Citing Articles

Exploring the Impact of Semaglutide on Cognitive Function and Anxiety-Related Behaviors in a Murine Model of Alzheimer's Disease.

Boboc I, Dumitrelea P, Meca A, Mititelu-Tartau L, Bogdan M Biomedicines. 2025; 12(12.

PMID: 39767596 PMC: 11673043. DOI: 10.3390/biomedicines12122689.

MAFLD Pandemic: Updates in Pharmacotherapeutic Approach Development.

Khaznadar F, Khaznadar O, Petrovic A, Hefer M, Gjoni F, Gjoni S Curr Issues Mol Biol. 2024; 46(7):6300-6314.

PMID: 39057018 PMC: 11275123. DOI: 10.3390/cimb46070376.

References

Ferraioli G, Soares Monteiro L . Ultrasound-based techniques for the diagnosis of liver steatosis. World J Gastroenterol. 2019; 25(40):6053-6062. PMC: 6824276. DOI: 10.3748/wjg.v25.i40.6053. View

Knudsen L, Lau J . The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019; 10:155. PMC: 6474072. DOI: 10.3389/fendo.2019.00155. View

Leung J, Loong T, Wei J, Wong G, Chan A, Choi P . Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology. 2016; 65(1):54-64. DOI: 10.1002/hep.28697. View

Hallsworth K, Adams L . Lifestyle modification in NAFLD/NASH: Facts and figures. JHEP Rep. 2020; 1(6):468-479. PMC: 7005657. DOI: 10.1016/j.jhepr.2019.10.008. View

Pontes-da-Silva R, Marinho T, Cardoso L, Mandarim-de-Lacerda C, Aguila M . Obese mice weight loss role on nonalcoholic fatty liver disease and endoplasmic reticulum stress treated by a GLP-1 receptor agonist. Int J Obes (Lond). 2021; 46(1):21-29. DOI: 10.1038/s41366-021-00955-7. View

Arai T, Atsukawa M, Tsubota A, Ono H, Kawano T, Yoshida Y . Efficacy and safety of oral semaglutide in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study. JGH Open. 2022; 6(7):503-511. PMC: 9260206. DOI: 10.1002/jgh3.12780. View

Mundi M, Velapati S, Patel J, Kellogg T, Abu Dayyeh B, Hurt R . Evolution of NAFLD and Its Management. Nutr Clin Pract. 2019; 35(1):72-84. DOI: 10.1002/ncp.10449. View

Davies M, Faerch L, Jeppesen O, Pakseresht A, Pedersen S, Perreault L . Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021; 397(10278):971-984. DOI: 10.1016/S0140-6736(21)00213-0. View

Nauck M, Quast D . Cardiovascular Safety and Benefits of Semaglutide in Patients With Type 2 Diabetes: Findings From SUSTAIN 6 and PIONEER 6. Front Endocrinol (Lausanne). 2021; 12:645566. PMC: 8039387. DOI: 10.3389/fendo.2021.645566. View

10.

Vernon G, Baranova A, Younossi Z . Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011; 34(3):274-85. DOI: 10.1111/j.1365-2036.2011.04724.x. View

11.

Pyke C, Heller R, Kirk R, Orskov C, Reedtz-Runge S, Kaastrup P . GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014; 155(4):1280-90. DOI: 10.1210/en.2013-1934. View

12.

Gibbons C, Blundell J, Hoff S, Dahl K, Bauer R, Baekdal T . Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes. Diabetes Obes Metab. 2020; 23(2):581-588. PMC: 7839771. DOI: 10.1111/dom.14255. View

13.

Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S . Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2014; 61(5):1547-54. DOI: 10.1002/hep.27368. View

14.

Flint A, Andersen G, Hockings P, Johansson L, Morsing A, Sundby Palle M . Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2021; 54(9):1150-1161. PMC: 9292692. DOI: 10.1111/apt.16608. View

15.

Younossi Z, Golabi P, Paik J, Henry A, Van Dongen C, Henry L . The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023; 77(4):1335-1347. PMC: 10026948. DOI: 10.1097/HEP.0000000000000004. View

16.

Paradies G, Paradies V, Ruggiero F, Petrosillo G . Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease. World J Gastroenterol. 2014; 20(39):14205-18. PMC: 4202349. DOI: 10.3748/wjg.v20.i39.14205. View

17.

Baekdal T, Thomsen M, Kupcova V, Hansen C, Anderson T . Pharmacokinetics, Safety, and Tolerability of Oral Semaglutide in Subjects With Hepatic Impairment. J Clin Pharmacol. 2018; 58(10):1314-1323. PMC: 6175428. DOI: 10.1002/jcph.1131. View

18.

Weghuber D, Barrett T, Barrientos-Perez M, Gies I, Hesse D, Jeppesen O . Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022; 387(24):2245-2257. PMC: 9997064. DOI: 10.1056/NEJMoa2208601. View

19.

Newsome P, Francque S, Harrison S, Ratziu V, Van Gaal L, Calanna S . Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity. Aliment Pharmacol Ther. 2019; 50(2):193-203. PMC: 6617813. DOI: 10.1111/apt.15316. View

20.

Younossi Z, Koenig A, Abdelatif D, Fazel Y, Henry L, Wymer M . Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2015; 64(1):73-84. DOI: 10.1002/hep.28431. View