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
Abstract
AIM: To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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Strong associations between subsequent reductions in body weight, HbA1c, and visceral fat and reductions in inflammatory biomarkers were found in several of the trials included in this evaluation.
“Strong associations between subsequent reductions in body weight, HbA1c, and visceral fat and reductions in inflammatory biomarkers were found in several of the trials included in our evaluation (7, 28, 35, 51, 52).”
In comparison to metformin and other medications, GLP-1 RAs dramatically decreased hepatic enzymes, liver fat content, and inflammatory markers in a number of trials that specifically investigated T2D patients with NAFLD.
“In comparison to metformin and other medications, GLP-1 RAs dramatically decreased hepatic enzymes, liver fat content, and inflammatory markers in a number of trials that specifically investigated T2D patients with non-alcoholic fatty liver disease (NAFLD) (13, 28, 40).”
Exenatide reduces liver fat content and epicardial fat in obese patients with uncontrolled T2DM, not associated with significant HbA1c reduction but with significant relation with weight loss.
“Similarly, in another trial using RM, in obese patients with uncontrolled T2DM, exenatide reduced liver fat content and epicardial fat, not associated with a significant HbA1c reduction, but with a significant relation with weight loss when compared with reference treatment (sulphonylureas or repaglinide alone or in combination with metformin) [127].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [127]
Exenatide induced reduction of EAT and hepatic triglyceride content.
“One study showed that exenatide, a first generation weekly GLP-1 receptor, induced the reduction of EAT and hepatic triglyceride content [27].”
From Effects of Semaglutide Versus Dulaglutide on Epicardial Fat Thickness in Subjects with Type 2 Diabetes and Obesity (2020) · cites this paper as [27]
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- Authors
- Dutour, A., Abdesselam, I., Ancel, P., Kober, F., Mrad, G., Darmon, P., Ronsin, O., Pradel, V., Lesavre, N., Martin, J. C., Jacquier, A., Lefur, Y., Bernard, M., & Gaborit, B.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Department of Endocrinology Metabolic Diseases and Nutrition, Pole Endo Marseille France
- Aix-Marseille Université (FR)
- Aix Marseille Université Marseille France
- Corresponding author
- Gaborit, B.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2016-05-31
- Volume
- 18
- Issue
- 9
- Pages
- 882-891
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2337473245
- Cited by
- 262
- References
- 51
- Citations by year
- 2026: 22 · 2025: 35 · 2024: 28 · 2023: 38 · 2022: 35 · 2021: 31 · 2020: 29 · 2019: 18 · 2018: 13 · 2017: 8 · 2016: 4
- FWCI
- 14.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- HAL AMU (submittedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- exenatide, GLP-1 receptor agonists, hepatic steatosis, epicardial adipose tissue, ectopic fat, type 2 diabetes, obesity, hepatic triglyceride content, myocardial triglyceride content, weight loss, insulin resistance, adiponectin, HbA1c, 1H NMR
- MeSH terms
- Exenatide, Adipose Tissue, Diabetes Mellitus, Type 2, Fatty Liver, Female, Heart, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Myocardium, Obesity, Pancreas, Peptides, Pericardium, Triglycerides, Venoms, Treatment Outcome, Postprandial Period, Proton Magnetic Resonance Spectroscopy
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