title: Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes.
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).
authors.affiliation: Diabetes and Endocrinology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Padma
authors.initials: P
authors.lastname: Sathyanarayana
authors.forename: Medhavi
authors.initials: M
authors.lastname: Jogi
authors.forename: Raja
authors.initials: R
authors.lastname: Muthupillai
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Krishnamurthy
authors.forename: Susan L
authors.initials: SL
authors.lastname: Samson
authors.forename: Mandeep
authors.initials: M
authors.lastname: Bajaj
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D000077205:Pioglitazone; D018027:Receptors, Glucagon / Q000819:agonists; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D015415:Biomarkers; D001786:Blood Glucose; D000077270:Exenatide; D005230:Fatty Acids, Nonesterified; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D047495:PPAR gamma; D010455:Peptides; D000077205:Pioglitazone; D018027:Receptors, Glucagon; D045162:Thiazolidinediones; D014280:Triglycerides; D014688:Venoms; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human