A double-blind, placebo-controlled, randomised trial to assess the effect of liraglutide on ectopic fat accumulation in South Asian type 2 diabetes patients
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Abstract Background South Asians have a high risk to develop type 2 diabetes, which may be related to substantial ectopic fat deposition. Since glucagon-like peptide-1 analogues can reduce ectopic fat accumulation, the aim of the present study was to assess the effect of treatment with liraglutide for 26 weeks on ectopic fat deposition and HbA1c in South Asian patients with type 2 diabetes. Methods In a placebo-controlled trial, 47 South Asian patients with type 2 diabetes were randomly assigned to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after 26 weeks of treatment we assessed abdominal subcutaneous, visceral, epicardial and paracardial adipose tissue volume using MRI. Furthermore, myocardial and hepatic triglyceride content were examined with proton magnetic resonance spectroscopy. Results In the intention-to-treat analysis, liraglutide decreased body weight compared to placebo (− 3.9 ± 3.6 kg vs − 0.6 ± 2.2 kg; mean change from baseline (liraglutide vs placebo): − 3.5 kg; 95% CI [− 5.3, − 1.8]) without significant effects on the different adipose tissue compartments. HbA1c was decreased in both groups without between group differences. In the per-protocol analysis, liraglutide did decrease visceral adipose tissue volume compared to placebo (− 23 ± 27 cm 2 vs − 2 ± 17 cm 2 ; mean change from baseline (liraglutide vs placebo): − 17 cm 2 ; 95% CI [− 32, − 3]). Furthermore, HbA1c was decreased by liraglutide compared to placebo (− 1.0 ± 0.8% (− 10.5 ± 9.1 mmol/mol)) vs (− 0.6 ± 0.8% (− 6.1 ± 8.8 mmol/mol)), with a between group difference (mean change from baseline (liraglutide vs placebo): − 0.6% (− 6.5 mmol/mol); 95% CI [− 1.1, − 0.1 (− 11.5, − 1.5)]). Interestingly, the decrease of visceral adipose tissue volume was associated with the reduction of HbA1c (β: 0.165 mmol/mol (0.015%) per 1 cm 2 decrease of visceral adipose tissue volume; 95% CI [0.062, 0.267 (0.006, 0.024%)]). Conclusions While the intention-to-treat analysis did not show effects of liraglutide on ectopic fat and HbA1c, per-protocol analysis showed that liraglutide decreases visceral adipose tissue volume, which was associated with improved glycaemic control in South Asians. Trial registration NCT02660047 (clinicaltrials.gov). Registered 21 January 2016
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Intention-to-treat analysis does not reveal a significant effect of liraglutide on most adipose tissue compartments including EAT.
“In another, the intention-to-treat analysis did not reveal a significant effect of liraglutide on most of adipose tissue compartments including EAT [125].”
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 [125]
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- Authors
- van Eyk, H. J., Paiman, E. H. M., Bizino, M. B., de Heer, P., Geelhoed-Duijvestijn, P. H., Kharagjitsingh, A. V., Smit, J. W. A., Lamb, H. J., Rensen, P. C. N., & Jazet, I. M.
- Affiliations
- Leiden University Medical Center (NL)
- Medisch Centrum Haaglanden (NL)
- Radboud University Medical Center (NL)
- ORCID
- Venue
- Cardiovascular Diabetology
- Published
- 2019-07-09
- Volume
- 18
- Issue
- 1
- Pages
- 87-87
- ISSN
- 1475-2840 (ISSN-L)
- PMC
- PMC6615254
- OpenAlex
- W2958641751
- Cited by
- 90
- References
- 47
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 17 · 2023: 14 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 2
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cardiovascular Diabetology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Novo Nordisk
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- liraglutide, type 2 diabetes, South Asian patients, ectopic fat deposition, visceral adipose tissue, hepatic triglyceride content, myocardial triglyceride content, epicardial adipose tissue, subcutaneous adipose tissue, HbA1c, weight loss, GLP-1 receptor agonists
- MeSH terms
- Liraglutide, Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Middle Aged, Netherlands, Time Factors, Biomarkers, Treatment Outcome, Asian People, Intra-Abdominal Fat, Adiposity, Incretins
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