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World J Gastroenterol. Jun 21, 2014; 20(23): 7356-7365
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7356
Incretin based therapies: A novel treatment approach for non-alcoholic fatty liver disease
Kristina Blaslov, Tomislav Bulum, Karin Zibar, Lea Duvnjak
Kristina Blaslov, Tomislav Bulum, Karin Zibar, Lea Duvnjak, Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Author contributions: All the authors contributed equally to this work; Blaslov K and Bulum T designed the research; Blaslov K, Bulum T, Zibar K and Duvnjak L acquisited data and did the critical analysis and the data interpretation; Bulum T and Zibar K drafted the manuscript; Blaslov K, Bulum T, Zibar K and Duvnjak L wrote the paper.
Correspondence to: Kristina Blaslov, MD, Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, School of Medicine, University of Zagreb, Dugi dol 4a, 10000 Zagreb, Croatia. kblaslov@gmail.com
Telephone: +385-1-2353829 Fax: +385-1-2353829
Received: October 13, 2013
Revised: December 7, 2013
Accepted: January 8, 2014
Published online: June 21, 2014
Abstract

Non-alcoholic fatty liver disease is considered a hepatic manifestation of metabolic syndrome (MS). The current treatment of non-alcoholic fatty liver disease (NAFLD) principally includes amelioration of MS components by lifestyle modifications but the lack of success in their implementation and sustainment arises the need for effective pharmacological agent in fatty liver treatment. Incretins are gut derived hormones secreted into the circulation in response to nutrient ingestion that enhances glucose-stimulated insulin secretion. Glucagon-like peptide-1 (GLP-1) is the most important incretin. Its receptor agonist and inhibitors of dipeptidyl peptidase-4 (DPP-4) are used in treatment of type 2 diabetes mellitus. DPP-4 serum activity and hepatic expression are shown to be elevated in several hepatic diseases. There are several experimental and clinical trials exploring the efficacy of incretin based therapies in NAFLD treatment. They suggest that GLP-1 analogues might have beneficial effect on hepatic steatosis acting as insulin sensitizers and directly by stimulating GLP-1 receptors expressed on hepatocytes. The use of DPP-4 inhibitors also results in hepatic fat reduction but the mechanism of action remains unclear. There is growing evidence that incretin based therapies have beneficial effects on hepatocytes, however further study analysis are needed to assess the long term effect of incretin based therapies on NAFLD.

Keywords: Non-alcoholic fatty liver disease, Insulin resistance, Glucagon-like peptide-1, Dipeptidyl peptidase-4, Metabolic syndrome

Core tip: Insulin resistance is considered a fundamental problem in the genesis of hepatic steatosis and the pathophysiology of its development. In this review we discussed the role of incretin based therapies, including glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors as a potential novel agents in non-alcoholic fatty liver disease treatment comprising experimental and clinical data available so far which generally suggest that GLP-1 analogues as well as DPP-4 inhibitors might be involved in direct pathways of liver fat elimination. To the best of our knowledge, this is the first review comprising all the data about incretin based therapies in fatty liver treatment.