Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy.
To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores.



A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment.



The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m(2) . Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (-0.7 ± 0.3% vs. -0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (-5.5 ± 1.2 kg vs. -0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (-8.8 ± 2.1%) and HTGC (-23.8 ± 9.5%), compared with the reference treatment (EAT: -1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively).



Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France.|Aix Marseille Université, Marseille, France.|Department of Endocrinology, Metabolic Diseases and Nutrition, Pole Endo, Marseille, France.
A
A
Dutour
Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France.|Aix Marseille Université, Marseille, France.|Centre de Résonance Magnétique Biologique et Médicale, CNRS UMR 7339, Marseille, France.
I
I
Abdesselam
Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France.|Aix Marseille Université, Marseille, France.
P
P
Ancel
Aix Marseille Université, Marseille, France.|Centre de Résonance Magnétique Biologique et Médicale, CNRS UMR 7339, Marseille, France.
F
F
Kober
Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France.
G
G
Mrad
Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France.|Aix Marseille Université, Marseille, France.|Department of Endocrinology, Metabolic Diseases and Nutrition, Pole Endo, Marseille, France.
P
P
Darmon
Department of Endocrinology, Metabolic Diseases and Nutrition, Pole Endo, Marseille, France.
O
O
Ronsin
Aix Marseille Université, Marseille, France.|Statistics Department, Assistance Publique Hôpitaux Marseille, CHU Sainte Marguerite, Marseille, France.
V
V
Pradel
Aix Marseille Université, Marseille, France.|Centre d'investigation Clinique, 1409, Assistance Publique Hôpitaux de Marseille, CHU Nord, Marseille, France.
N
N
Lesavre
Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France.|Aix Marseille Université, Marseille, France.
J C
JC
Martin
Aix Marseille Université, Marseille, France.|Centre de Résonance Magnétique Biologique et Médicale, CNRS UMR 7339, Marseille, France.|Radiology Department, CHU La Timone, Marseille, France.
A
A
Jacquier
Aix Marseille Université, Marseille, France.|Centre de Résonance Magnétique Biologique et Médicale, CNRS UMR 7339, Marseille, France.
Y
Y
Lefur
Aix Marseille Université, Marseille, France.|Centre de Résonance Magnétique Biologique et Médicale, CNRS UMR 7339, Marseille, France.
M
M
Bernard
Inserm U1062, Inra U1260, Faculté de Médecine, 13385, Marseille, France.|Aix Marseille Université, Marseille, France.|Department of Endocrinology, Metabolic Diseases and Nutrition, Pole Endo, Marseille, France.
B
B
Gaborit
D000273:Adipose Tissue / Q000000981:diagnostic imaging* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D005234:Fatty Liver / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use*; D010496:Pericardium / Q000000981:diagnostic imaging* / Q000378:metabolism; D019518:Postprandial Period; D066244:Proton Magnetic Resonance Spectroscopy; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism; D014688:Venoms / Q000627:therapeutic use*
D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D014280:Triglycerides; D014688:Venoms; C517652:hemoglobin A1c protein, human
epicardial adipose tissue; glucagon-like peptide 1 receptor agonist; hepatic triglyceride content; magnetic resonance imaging; myocardial triglyceride content; obesity; pancreatic triglyceride content; proton magnetic resonance spectroscopy; type 2 diabetes