EFFICACY AND SAFETY OF SEMAGLUTIDE IN NON-ALCOHOLIC FATTY LIVER DISEASE
Main Article Content
Keywords
Efficacy, Safety, Semaglutide, Non-Alcoholic Fatty Liver Disease
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with an estimated worldwide prevalence of 32.4%. The prevalence and disease burden of NAFLD are projected to exponentially increase, with mathematical models forecasting a 168% increase in the incidence of decompensated cirrhosis and a 178% increase in NAFLD-related deaths between 2015 and 2030.
Objective: To determine the Efficacy and Safety of Semaglutide in Non-Alcoholic Fatty Liver Disease
Methodology: This clinical based study was carried out at the Department of medicine, Bolan medical college/ Bolan medical complex hospital Quetta. The study duration was one year from January 2023 to January 2024. This study approval was given by the ethical committee of the hospital. To diagnose liver inflammation or injury, ALT and AST enzymes were measured. The initial dose escalation schedule for semaglutide was followed subcutaneously by patients. During the 1st four weeks, 0.25 mg dose was given once a week. Then the dose was increased to 0.5 mg during 5 to 8 weeks. It was further followed by an increase to 1mg in the 9th week and onwards. All the data was analyzed by using SPSS version 23.
Results: In the current study, a total of 40 patients were included. There were 24 (60%) males and 16 (40%) females in our study. The mean (SD) of the patients was 48 (±12) years with minimum age of 45 and maximum age of 60 years. Significant improvements were observed in triglycerides (p = 0.002), LDL cholesterol (p = 0.002), HDL cholesterol (p = 0.000), body weight (p = 0.03), fasting plasma glucose (<0.001), BMI (p = 0.001) and HbA1c (p = 0.42). Reductions in ALT (p = 0.0001) and AST (p = 0.13) in liver function tests.
Conclusion: Our study concludes that Semaglutide provides a therapeutic option for NAFLD, but still, collaborative efforts and modifications in lifestyle are required to lessen this burden on human health. An effective improvement was observed in different parameters by comparing Semaglutide activity with baseline measures
References
2. Cheemerla S, Balakrishnan M. Global Epidemiology of Chronic Liver Disease. Clin Liver Dis (Hoboken) 2021;17:365–370.
3. Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67:123–133.
4. Golabi P, Otgonsuren M, Cable R, Felix S, Koenig A, Sayiner M, Younossi ZM. Non-alcoholic Fatty Liver Disease (NAFLD) is associated with impairment of Health Related Quality of Life (HRQOL) Health Qual Life Outcomes. 2016;14:18.
5. Younossi ZM, Blissett D, Blissett R, Henry L, Stepanova M, Younossi Y, Racila A, Hunt S, Beckerman R. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64:1577–1586.
6. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterologyh. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142:1592–1609.
7. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313:2263–2273.
8. Ma J, Hwang SJ, Pedley A, Massaro JM, Hoffmann U, Chung RT, Benjamin EJ, Levy D, Fox CS, Long MT. Bi-directional analysis between fatty liver and cardiovascular disease risk factors. J Hepatol. 2017;66:390–397.
9. Gupta NA, Mells J, Dunham RM, Grakoui A, Handy J, Saxena NK, Anania FA. 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. 2010;51:1584–1592.
10. Dichtel LE. The Glucagon-Like Peptide-1 Receptor Agonist, Semaglutide, for the Treatment of Nonalcoholic Steatohepatitis. Hepatology. 2021;74:2290–2292.
11. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care. 2022;45:2753–2786.
12. Targher G, Mantovani A, Byrne CD. Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease. Lancet Gastroenterol Hepatol. 2023;8:179–191.
13. Nauck MA, Meier JJ. MANAGEMENT OF ENDOCRINE DISEASE: Are all GLP-1 agonists equal in the treatment of type 2 diabetes? Eur J Endocrinol. 2019;181:R211–R234.
14. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384:989–1002.
15. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375:1834–1844.
16. Dutta D, Kumar M, Shivaprasad KS, Kumar A, Sharma M. Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis. Diabetes Metab Syndr. 2022;16:102539.
17. Loomba R, Abdelmalek MF, Armstrong MJ, Jara M, Kjær MS, Krarup N, Lawitz E, Ratziu V, Sanyal AJ, Schattenberg JM, Newsome PN NN9931-4492 investigators. Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511–522.
18. Petzold G. Role of Ultrasound Methods for the Assessment of NAFLD. J Clin Med 2022;11(15).
19. Miller MJ, Harding-Theobald E, DiBattista JV, Zhao Z, Wijarnpreecha K, Lok AS, et al. Progression to cirrhosis is similar among all ages in nonalcoholic fatty liver disease, but liver-related events increase with age. Hepatol Commun 2023;7(6).
20. Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatol 2018;67(1):123–33.
21. Alkhouri N, Almomani A, Le P, Payne JY, Asaad I, Sakkal C, et al. The prevalence of alcoholic and nonalcoholic fatty liver disease in adolescents and young adults in the United States: analysis of the NHANES database. BMC Gastroenterol 2022;22(1).
22. Dufour JF, Scherer R, Balp MM, McKenna SJ, Janssens N, Lopez P, et al. The global epidemiology of nonalcoholic steatohepatitis (NASH) and associated risk factors–A targeted literature review. Endocr Metab Sci 2021;3.
23. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): A multicentre, randomised, placebo- controlled trial. Lancet. 2015;385(9972):956–65.
24. Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2021;384(12):1113–24.
25. Okamoto A, Yokokawa H, Nagamine T, Fukuda H, Hisaoka T, Naito T. Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists. J Diabetes Metab Disord 2021;20(2): 2121–8.
26. Nomoto H, Takahashi Y, Takano Y, Yokoyama H, Tsuchida K, Nagai S, et al. Effect of Switching to Once-Weekly Semaglutide on Non-Alcoholic Fatty Liver Disease: The SWITCH-SEMA 1 Subanalysis. Pharmaceutics 2023;15(8).
27. Bækdal TA, Thomsen M, Kupčová V, Hansen CW, Anderson TW. Pharmacokinetics, Safety, and Tolerability of Oral Semaglutide in Subjects with Hepatic Impairment. J Clin Pharmacol 2018; 58(10):1314–23.
28. Niu S, Chen S, Chen X, Ren Q, Yue L, Pan X, et al. Semaglutide ameliorates metabolism and hepatic outcomes in an NAFLD mouse model. Front Endocrinol (Lausanne) 2022;13.
29. Petrovic A, Igrec D, Rozac K, Bojanic K, Kuna L, Kolaric TO, et al. The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models of NAFLD. Curr Issues Mol Biol 2023;45(6):4544–56.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Taqdees Zahra
Assistant Professor, Department of Medicine, Bolan Medical College/ Bolan Medical Complex Hospital, Quetta - Pakistan
Tahira
Assistant Professor, Department of Medicine, Bolan Medical College/ Bolan Medical Complex Hospital, Quetta - Pakistan
Samreen Bugti
Assistant Professor, Department of Medicine, Bolan Medical College/ Bolan Medical Complex Hospital, Quetta - Pakistan
Tariq Mehmood
Medicine PGMI/Sheikh Khalifa Bin Zayyed al Nehan Hospital, Quetta - Pakistandr.sbugti@gmail.com