title: Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial.
abstract: 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.
  
  
  
  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, HbA1c7.3 ± 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.
  
  
  
  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.
  
  
  
  Twelve-week liraglutide or sitagliptin treatment does not reduce hepatic steatosis or fibrosis in type 2 diabetes.
  
  
  
  ClinicalTrials.gov NCT01744236 FUNDING : Funded by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282521 - the SAFEGUARD project.
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 (Room ZH 4A65), 1081 HV, Amsterdam, the Netherlands. mm.smits1@vumc.nl.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 (Room ZH 4A65), 1081 HV, Amsterdam, the Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: Tonneijck
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 (Room ZH 4A65), 1081 HV, Amsterdam, the Netherlands.
authors.forename: Marcel H A
authors.initials: MH
authors.lastname: Muskiet
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 (Room ZH 4A65), 1081 HV, Amsterdam, the Netherlands.
authors.forename: Mark H H
authors.initials: MH
authors.lastname: Kramer
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Center and Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Indra C
authors.initials: IC
authors.lastname: Pieters-van den Bos
authors.affiliation: Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands.|Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Trynke
authors.initials: T
authors.lastname: Hoekstra
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 (Room ZH 4A65), 1081 HV, Amsterdam, the Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 (Room ZH 4A65), 1081 HV, Amsterdam, the Netherlands.
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Djuna L
authors.initials: DL
authors.lastname: Cahen
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; D000067757:Glucagon-Like Peptide-1 Receptor
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D000068900:Sitagliptin Phosphate; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor
keywords: Dipeptidyl peptidase-4 inhibitor; Glucagon-like peptide-1 receptor agonist; Non-alcoholic fatty liver disease; Type 2 diabetes