Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists

PLoS One. 2012;7(12):e50117. doi: 10.1371/journal.pone.0050117. Epub 2012 Dec 6.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy ((1)H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA(1c) reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (-59.3, -16.5%). The relative reduction in IHL correlated with that in HbA(1)c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / drug effects
  • Adult
  • Blood Glucose / drug effects*
  • Body Mass Index
  • Body Weight
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Exenatide
  • Fatty Liver / drug therapy*
  • Fatty Liver / metabolism
  • Female
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Liraglutide
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Middle Aged
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Peptides / therapeutic use
  • Prospective Studies
  • Venoms / therapeutic use
  • Weight Loss / drug effects

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide

Grant support

Funding from medical charity Weight Matters was for £2500. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Please note this charity is a local charity set up by the investigators and the volunteers within the authors' hospital and they contributed £2500 towards cost of MRI scanning.