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

Abstract

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, HbA1c 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 (1H-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.

Keywords: Dipeptidyl peptidase-4 inhibitor; Glucagon-like peptide-1 receptor agonist; Non-alcoholic fatty liver disease; Type 2 diabetes.

Conflict of interest statement

Duality of interest statement

Through MD and MHHK, the VU University Medical Center received research grants from AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Sanofi. All other authors declare that there is no duality of interest associated with their contribution to this manuscript.

Contribution statement

MMS developed the study protocol, performed the measurements and analyses, and drafted the manuscript. LT performed measurements and made a substantial contribution to data interpretation and revision of the manuscript. MD developed the study protocol and was involved in the discussion. TH contributed to data analysis and interpretation, and critically revised the manuscript. MHAM, ICP-vdB, PJWP, MHHK, DHvR and DLC contributed to data interpretation and revised the manuscript. MMS and DHR had full access to all of the data and can take responsibility for the integrity of the data and the accuracy of the data analysis. All authors have approved the final version of this manuscript.

Figures

Fig. 1

Effects of treatment on 1H-MRS-measured hepatic fat content and calculated fibrosis. Effects of liraglutide, sitagliptin or placebo on hepatic endpoints. White bars, measurements at baseline; grey bars, measurements at 12 weeks. (a, b) Hepatic fat content as measured using 1H-MRS, with individual effects shown in (b). Markers of hepatic fibrosis: (c) NFS; (d) FIB-4; (e) APRI. Data are mean ± SEM. None of the effects was statistically significant (p < 0.05)