Effects of Combined Exenatide and Pioglitazone Therapy on Hepatic Fat Content in Type 2 Diabetes

Obesity (Silver Spring). 2011 Dec;19(12):2310-5. doi: 10.1038/oby.2011.152. Epub 2011 Jun 9.

Abstract

We examined the effects of combined pioglitazone (peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist) and exenatide (GLP-1 receptor agonist) therapy on hepatic fat content and plasma adiponectin levels in patients with type 2 diabetes (T2DM). Twenty-one T2DM patients (age = 52 ± 3 years, BMI = 32.0 ± 1.5, hemoglobin A(1c) (HbA(1c)) = 8.2 ± 0.4%) on diet and/or metformin received additional treatment with either pioglitazone 45 mg/day for 12 months (n = 10) or combined therapy with pioglitazone (45 mg/day) and exenatide (10 µg subcutaneously twice daily) for 12 months (n = 11). At baseline, hepatic fat content and plasma adiponectin levels were similar between the two treatment groups. Pioglitazone reduced fasting plasma glucose (FPG) (P < 0.05), fasting free fatty acid (FFA) (P < 0.05), and HbA(1c) (Δ = 1.0%, P < 0.01), while increasing plasma adiponectin concentration by 86% (P < 0.05). Hepatic fat (magnetic resonance spectroscopy (MRS)) was significantly reduced following pioglitazone treatment (11.0 ± 3.1 to 6.5 ± 1.9%, P < 0.05). Plasma triglyceride concentration decreased by 14% (P < 0.05) and body weight increased significantly (Δ = 3.7 kg). Combined pioglitazone and exenatide therapy was associated with a significantly greater increase in plasma adiponectin (Δ = 193%) and a significantly greater decrease in hepatic fat (12.1 ± 1.7 to 4.7 ± 1.3%) and plasma triglyceride (38%) vs. pioglitazone therapy despite the lack of a significant change in body weight (Δ = 0.2 kg). Hepatic injury biomarkers aspartate aminotransferase and alanine aminotransferase (ALT) were significantly decreased by both treatments; however, the reduction in ALT was significantly greater following combined pioglitazone and exenatide therapy. We conclude that combined in patients with T2DM, pioglitazone and exenatide therapy is associated with a greater reduction in hepatic fat content as compared to the addition of pioglitazone therapy (Δ = 61% vs. 41%, P < 0.05).

Publication types

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

MeSH terms

  • Adiponectin / blood
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Therapy, Combination
  • Exenatide
  • Fasting
  • Fatty Acids, Nonesterified / blood
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy
  • Metformin / therapeutic use
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy
  • Obesity / metabolism
  • PPAR gamma / agonists
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Pioglitazone
  • Receptors, Glucagon / agonists
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Triglycerides / blood
  • Venoms / pharmacology
  • Venoms / therapeutic use*

Substances

  • Adiponectin
  • Biomarkers
  • Blood Glucose
  • Fatty Acids, Nonesterified
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • PPAR gamma
  • Peptides
  • Receptors, Glucagon
  • Thiazolidinediones
  • Triglycerides
  • Venoms
  • hemoglobin A1c protein, human
  • Metformin
  • Exenatide
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Pioglitazone