The efficacy of antidiabetic agents for the treatment of non-alcoholic fatty liver disease (NAFLD) remains unclear.
To conduct a meta-analysis to study the efficacy of pioglitazone and three novel anti-diabetic agents: glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors in treating NAFLD.
Online databases were searched in May 2020 for randomized clinical trials. Results from random-effects meta-analysis are presented as weighted mean differences (WMDs) or standard mean differences (SMDs) and corresponding 95% confidence intervals (CIs).
Twenty-six studies (n=946 NAFLD patients) were included. Reductions in ALT were seen with all four drugs: pioglitazone (MD -38.41, p<0.001), SGLT2 inhibitors (MD -16.17, p<0.001), GLP-1 agonists (MD -27.98, p=0.04) and DPP-4 inhibitors (MD -7.41, p<0.001). Pioglitazone (SMD -1.01; p<0.001) and GLP-1 agonists (SMD -2.53, p=0.03) also demonstrated significant improvements in liver steatosis. SGLT2 inhibitors (SMD -4.64, p=0.06) and DPP-4 (SMD -2.49, p=0.06) inhibitors trended towards reduced steatosis; however, these results were non-significant.
Pioglitazone demonstrates significant improvements in transaminases and liver histology in both diabetic and non-diabetic NAFLD patients. Early evidence from diabetic NAFLD patients suggests that novel antidiabetics may lead to improvements in liver enzymes and hepatic steatosis, and this should encourage further research into possible utility of these drugs in treating NAFLD.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Digestive and Liver Disease
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: an updated systematic review of randomized controlled trials.Diabetes Metab. 2020; (S1262-3636(20)30002-1)
- Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis.J Gastroenterol Hepatol. 2016; 31: 936-944
- Nonalcoholic fatty liver disease and risk of incident type 2 diabetes mellitus: a meta-analysis.Diabetes Care. 2018; 41: 372-382
- The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases.Hepatology. 2018; 67: 328-357
- Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial.Diabetologia. 2018; 61: 2155-2163
- Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24-week, open-label, active-controlled trial.Diabetes Care. 2017; 40: 1364-1372
- Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial).Diabetes care. 2018; 41: 1801-1808
- The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.Ann Intern Med. 2015; 162: 777-784
- Higgins JPT Thomas J Chandler J Cochrane handbook for systematic reviews of interventions version 6.0 (updated July 2019). Cochrane, 2019 (Available from:)
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560
- The effect of pioglitazone and metformin on liver function tests, insulin resistance, and liver fat content in nonalcoholic Fatty liver disease: a randomized double blinded clinical trial.Hepat Mon. 2013; 13: e9270
- A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis.Hepatology. 2004; 39: 188-196
- The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis.Hepatology. 2007; 46: 424-429
- Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non‐alcoholic fatty liver disease: a prospective randomized controlled pilot study.Diabetes Obes Metab. 2018; 20: 438-442
- Sitagliptin vs. placebo for non-alcoholic fatty liver disease: a randomized controlled trial.J Hepatol. 2016; 65: 369-376
- Short article: a randomized-controlled study of sitagliptin for treating diabetes mellitus complicated by nonalcoholic fatty liver disease.Eur J Gastroenterol Hepatol. 2017; 29: 297-301
- Effect of vildagliptin on hepatic steatosis.The J Clin Endocrinol Metab. 2015; 100: 1578-1585
- Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study.Lancet. 2016; 387: 679-690
- PDG2 efficacy of pioglitazone in improving liver histology scores of patients with non-alcoholic fatty liver disease: a systematic-review and meta-analysis.Value Health. 2019; 22: S163
- Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis.Aliment Pharmacol Ther. 2011; 35: 66-75
- Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis.JAMA Intern Med. 2017; 177: 633-640
- The effect of antidiabetic medications on non-alcoholic fatty liver disease (NAFLD).Hormones. 2018; 17: 219-229
Published online: September 08, 2020
Accepted: August 16, 2020
Received: April 25, 2020
© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.