Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes

Abstract

BackgroundThe aim of this study was to investigate the efficacy of exenatide and insulin glargine in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).MethodsWe performed a 24‐week randomized controlled multicentre clinical trial. Seventy‐six patients were randomly assigned 1:1 to receive exenatide or insulin glargine treatment. The endpoints included changes in liver fat content (LFC), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) measured by magnetic resonance spectroscopy, blood glucose, liver enzymes, lipid profile, body weight, and Fibrosis‐4 index (FIB‐4).ResultsLFC, VAT, SAT, and FIB‐4 were significantly reduced after exenatide treatment (ΔLFC, −17.55 ± 12.93%; ΔVAT, −43.57 ± 68.20 cm2; ΔSAT, −28.44 ± 51.48 cm2; ΔFIB‐4, −0.10 ± 0.26; all P < .05). In comparison, only LFC (ΔLFC, −10.49 ± 11.38%; P < .05), and not VAT, SAT, or FIB‐4 index (all P > .05), was reduced after insulin glargine treatment. Moreover, exenatide treatment resulted in greater reductions in alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transpeptidase (GGT) than insulin glargine (P < 0.05). The body weight, waist circumference, postprandial plasma glucose, and low‐density lipoprotein cholesterol (LDL‐C) in the exenatide group also presented greater reductions than the insulin glargine group (P < .05). The proportion of adverse events were comparable between the two groups.ConclusionBoth exenatide and insulin glargine reduced LFC in patients with drug‐naive T2DM and NAFLD; however, exenatide showed greater reductions in body weight, visceral fat area, liver enzymes, FIB‐4, postprandial plasma glucose, and LDL‐C.

Nonalcoholic fatty liver disease and the risk of metabolic comorbidities: how to manage in clinical practice

“…Similar outcomes have been reported with other GLP-1 agonists [32]. A trial of exenatide versus insulin therapy during eight weeks was associated with greater reversal of liver fat (assessed by ultrasound) [39], and comparable results were recently reported though liver fat was assessed by MRS (magnetic resonance spectroscopy) after 24 weeks treatment [40]. Regarding novel agents, GLP-1/glucose-dependent insulinotropic peptide receptors dual agonist improves NASH and liver regeneration in mice [41] and significantly decreased fibrosis biomarkers and increased adiponectin in patients with T2DM [42].…”

“…and NAFLD [40]. DPP-4 inhibitors (sitagliptin, linagliptin, vildagliptin, saxagliptin, teneligliptin, and alogliptin) work by blocking the enzyme that breaks down GLP-1, enhancing the effects and duration of incretins [45].…”

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials

“…Figure S1 shows the results of the literature research and study selection. We initially identified 15 potentially relevant RCTs from PubMed, Scopus and ClinicalTrials.Gov databases until to 15 December 2020 [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. After examining the full text of these 15 articles, we excluded four studies [35][36][37][38] because of unsatisfactory inclusion criteria or unsatisfactory outcome measures, as specified in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.…”

Comparison of the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Metabolic Associated Fatty Liver Disease: Updated Systematic Review and Meta-Analysis

“…Only Armstrong et al ( 19 ) used histology biopsy to estimate the severity of MAFLD. We found that methods for non-invasively assessing liver fat content varied by study, with magnetic resonance imaging (MRI) used by Khoo ( 21 , 22 ) and Yan ( 25 ), whereas Zhang and Liu ( 23 , 26 ) used 1 H-MRS. Shao ( 24 ) and Feng ( 20 ) used ultrasound imaging to assess liver fat content and stiffness. In addition, in control group, one study used liraglutide-placebo, one study used gliclazide, two studies used lifestyle modification, three studies used insulin therapy (both intensive insulin therapy or insulin plus metformin) and one study used pioglitazone plus metformin.…”