Effect of vildagliptin on hepatic steatosis

J Clin Endocrinol Metab. 2015 Apr;100(4):1578-85. doi: 10.1210/jc.2014-3794. Epub 2015 Feb 9.

Abstract

Context: 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.

Design: This was a 6-month, randomized, double-blind, placebo-controlled trial.

Setting: This was an outpatient study at a university clinical research center.

Patients: Individuals with type 2 diabetes (n = 44) and glycated hemoglobin ≤ 7.6% on stable metformin therapy were included.

Intervention: Intervention was vildagliptin 50 mg twice a day or placebo over 6 months.

Main outcome measures: 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.

Trial registration: ClinicalTrials.gov NCT01356381.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Aged
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Administration Schedule
  • Fatty Liver / drug therapy*
  • Fatty Liver / metabolism
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Nitriles / administration & dosage
  • Nitriles / therapeutic use*
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / therapeutic use*
  • Triglycerides / metabolism*
  • Vildagliptin

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Nitriles
  • Pyrrolidines
  • Triglycerides
  • hemoglobin A1c protein, human
  • Metformin
  • Vildagliptin
  • Adamantane

Associated data

  • ClinicalTrials.gov/NCT01356381