title: Effect of vildagliptin on hepatic steatosis.
abstract: BACKGROUND
  Although dipeptidyl-peptidase-4 inhibitors exert their major action via an incretin mechanism, a favorable effect of vildagliptin on lipid metabolism remains unexplained.
  
  
  OBJECTIVE
  The objective was to examine hepatic triglyceride levels and insulin sensitivity on vildagliptin.
  
  
  METHODS
  This was a 6-month, randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  This was an outpatient study at a university clinical research center.
  
  
  METHODS
  Individuals with type 2 diabetes (n = 44) and glycated hemoglobin ≤ 7.6% on stable metformin therapy were included.
  
  
  METHODS
  Intervention was vildagliptin 50 mg twice a day or placebo over 6 months.
  
  
  METHODS
  Main outcome measures were hepatic triglyceride levels and insulin sensitivity.
  
  
  RESULTS
  Mean fasting liver triglyceride content decreased by 27% with vildagliptin, from 7.3 ± 1.0% (baseline) to 5.3 ± 0.9% (endpoint). There was no change in the placebo group. The between-group difference in change from baseline was significant (P = .013). Mean fasting plasma glucose concentration decreased over the study period with vildagliptin vs placebo by -1.0 mmol/L (P = .018), and there was a positive correlation between these decrements and liver triglyceride in the vildagliptin group at 3 months (r = 0.47; P = .02) and 6 months (r = 0.44; P = .03). Plasma alanine aminotransferase fell from 27.2 ± 2.8 to 20.3 ± 1.4 IU/L in the vildagliptin group (P = .0007), and there was a correlation between the decrements in alanine aminotransferase and liver triglyceride (r = 0.83; P < .0001). Insulin sensitivity during the euglycemic clamp was similar in each group at baseline (3.24 ± 0.30 vs 3.19 ± 0.38 mg/kg/min) and did not change (adjusted mean change of 0.26 ± 0.22 vs 0.32 ± 0.22 mg/kg/min; P = .86). Mean body weight decreased by 1.6 ± 0.5 vs 0.4 ± 0.5 kg in the vildagliptin and placebo groups, respectively (P = .08).
  
  
  CONCLUSIONS
  This study demonstrates that the dipeptidyl-peptidase-4 inhibitor vildagliptin brings about a clinically significant decrease in hepatic triglyceride levels during 6 months of therapy unrelated to change in body weight. There was no change in peripheral insulin sensitivity.
authors: Newcastle Magnetic Resonance Centre (M.M., K.G.H., F.E.S., P.E.T., A.A.-M., R.T.), Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom; Novartis Pharma AG (A.S.), CH-4056 Basel, Switzerland; and Novartis Pharmaceutical (J.E.F.), East Hanover, New Jersey 07936.
authors: Mavin
authors: M
authors: Macauley
authors: Kieren G
authors: KG
authors: Hollingsworth
authors: Fiona E
authors: FE
authors: Smith
authors: Peter E
authors: PE
authors: Thelwall
authors: Ahmad
authors: A
authors: Al-Mrabeh
authors: Anja
authors: A
authors: Schweizer
authors: James E
authors: JE
authors: Foley
authors: Roy
authors: R
authors: Taylor
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism*; D000077597:Vildagliptin
chemical_list: D000218:Adamantane; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D009570:Nitriles; D011759:Pyrrolidines; D014280:Triglycerides; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human