Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: a randomized control trial
Open accessAbstract
Liraglutide, an analogue of human glucagon-like peptide 1, reduces cardiovascular events in patients with type 2 diabetes; however, it has still been unknown by which mechanisms liraglutide could reduce cardiovascular events. Type 2 diabetic patients with insulin treatment were enrolled in this randomized, open-label, comparative study. Participants were randomly assigned to liraglutide plus insulin (liraglutide group) and insulin treatment (control group) at 1:1 allocation. Primary endpoint was the change in viscera fat are (VFA, cm2) at 24 weeks. Liver attenuation index (LAI) measured by abdominal computed tomography, urinary albumin-to-creatinine ratio (ACR, mg/g), and C-reactive protein (CRP) levels, skeletal muscle index (SMI), and quality of life (QOL) related to diabetes treatment were also determined. Seventeen patients (8; liraglutide group, 9; control group, mean age 59 ± 13 years; 53% female) completed this study. Liraglutide treatment significantly reduced VFA at 24 weeks; whereas, SFA was unchanged. ACR, LAI, and CRP levels were significantly reduced by liraglutide at 24 weeks and there was no difference in SMI between the two groups. Changes in VFA from baseline to 24 weeks were significantly associated with those in LAI, albuminuria, and HbA1c. Liraglutide treatment significantly improved QOL scores associated with anxiety and dissatisfaction with treatment and satisfaction with treatment. No severe adverse events were observed in both groups. Our data suggest that liraglutide could reduce visceral adiposity in parallel with attenuation of hepatic fat accumulation, albuminuria and micro-inflammation and improve QOL related to diabetes care in insulin-treated patients with type 2 diabetes.
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Individual randomized controlled trial findings on the effects of GLP-1 receptor agonists on inflammatory biomarkers are inconsistent.
“The findings, however, have been inconsistent. Some studies report significant reductions in TNF-α and CRP with GLP-1 RA therapy compared to placebo or other antidiabetic medications (6, 15, 17, 18), while others show non-significant or conflicting results (19, 20).”
From Inflammatory biomarker response to GLP-1 receptor agonists versus other glucose-lowering medications in patients with type 2 diabetes: a systematic review and meta-analysis (2026) · cites this paper as [17]
The Efficacy and safety section reports that CRP fell significantly with liraglutide in this randomized trial, supporting the citing sentence’s example of a significant inflammatory-biomarker result. This paper does not report a TNF-α result or itself establish that findings across trials were inconsistent. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSome studies found that inflammatory markers rapidly decreased within weeks of starting GLP-1 RA treatment, prior to significant weight loss.
“Second, prior to significant weight loss, some studies found that inflammatory markers rapidly decreased within weeks of starting treatment (6, 17, 30).”
From Inflammatory biomarker response to GLP-1 receptor agonists versus other glucose-lowering medications in patients with type 2 diabetes: a systematic review and meta-analysis (2026) · cites this paper as [17]
The Efficacy and safety section (page unavailable) reports that C-reactive protein, an inflammatory marker, was significantly reduced at 12 weeks after liraglutide treatment. But Table 3 (page unavailable) shows body weight had already fallen by 12 weeks, and the paper does not establish that the CRP reduction preceded significant weight loss. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe comprehensive effect of reduced visceral fat and improvement in associated comorbidities was previously reported.
“The comprehensive effect of reduced visceral fat and improvement in associated comorbidities was previously reported (68, 73, 74).”
In this study, several studies found that improvements in inflammatory markers were accompanied by decreases in albuminuria.
“In our study, several studies found that improvements in inflammatory markers were accompanied by decreases in albuminuria (6, 15, 17, 18).”
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References 39 · Cited by 113
- Authors
- Bouchi, R., Nakano, Y., Fukuda, T., Takeuchi, T., Murakami, M., Minami, I., Izumiyama, H., Hashimoto, K., Yoshimoto, T., & Ogawa, Y.
- Affiliations
- Tokyo Medical and Dental University (JP)
- ORCID
- Venue
- Endocrine Journal
- Publisher
- Japan Endocrine Society
- Published
- 2017
- Volume
- 64
- Issue
- 3
- Pages
- 269-281
- ISSN
- 0918-8959 (ISSN-L)
- 1348-4540
- OpenAlex
- W2558199233
- Cited by
- 113
- References
- 39
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 8 · 2023: 15 · 2022: 14 · 2021: 10 · 2020: 12 · 2019: 15 · 2018: 13 · 2017: 4
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Endocrine Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Tokyo Medical and Dental University
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- liraglutide, type 2 diabetes, visceral fat, hepatic steatosis, albuminuria, microinflammation, C-reactive protein, insulin-treated patients, glucagon-like peptide-1 analogues, quality of life, skeletal muscle index, HbA1c
- MeSH terms
- Liraglutide, Albuminuria, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Diabetic Nephropathies, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Hypoglycemic Agents, Insulin, Japan, Male, Middle Aged, Quality of Life, Risk, Patient Satisfaction, Intra-Abdominal Fat, Adiposity, Diabetic Cardiomyopathies, Non-alcoholic Fatty Liver Disease
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