Journal Article

Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial

Smits, Mark M., Hoekstra, Trynke, Tonneijck, Lennart, van Raalte, Daniël H., Cahen, Djuna L., Kramer, Mark H. H., Diamant, Michaela, Pouwels, Petra J. W., Pieters-van den Bos, Indra C., Muskiet, Marcel H. A.

2016

Overview

Aims/hypothesis Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. Methods In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62.7 ± 6.9 years, HbA 1c 7.3 ± 0.7% or 56 ± 1 mmol/mol) were allocated to once daily liraglutide 1.8 mg ( n  = 17), sitagliptin 100 mg ( n  = 18) or matching placebos ( n  = 17) by computer generated numbers. Both participants and researchers were blinded to group assignment. Hepatic fat content was measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Hepatic fibrosis was estimated using three validated formulae. Results One patient dropped out in the sitagliptin group owing to dizziness, but no serious adverse events occurred. At week 12, no between-group differences in hepatic steatosis were found. Liraglutide reduced steatosis by 10% (20.9 ± 3.4% to 18.8 ± 3.3%), sitagliptin reduced steatosis by 12.1% (23.9 ± 3.0% to 21.0 ± 2.7%) and placebo lessened it by 9.5% (18.7 ± 2.7% to 16.9 ± 2.7%). Neither drug affected hepatic fibrosis scores compared with placebo. Conclusions/interpretation Twelve-week liraglutide or sitagliptin treatment does not reduce hepatic steatosis or fibrosis in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01744236 Funding Funded by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282521 – the SAFEGUARD project.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Adult / Aged / Diabetes / Diabetes Mellitus, Type 2 - drug therapy / Dipeptidyl-Peptidase IV Inhibitors / Female / Glucagon / Glucagon-Like Peptide 1 - metabolism / Glucagon-Like Peptide-1 Receptor - agonists / Human Physiology / Humans / Hypoglycemic Agents - therapeutic use / Insulin resistance / Internal Medicine / Liraglutide - therapeutic use / Liver Cirrhosis - drug therapy / Liver diseases / Magnetic Resonance Spectroscopy / Male / Medicine / Medicine & Public Health / Metabolic Diseases / Middle Aged / Peptides / Short Communication / Sitagliptin Phosphate - therapeutic use / Spectrum analysis