Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

Sofogianni, Areti; Filippidis, Athanasios; Chrysavgis, Lampros; Τζιόμαλος, Κωνσταντίνος

doi:10.4254/wjh.v12.i8.493

Cited by 25 publications

(22 citation statements)

References 64 publications

(111 reference statements)

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“…Liraglutide, semaglutide, and exenatide treatment all improved liver biomarkers ( 19 – 22 ), and liraglutide decreased histological inflammation in patients with biopsy-proven NASH ( 23 ). Some studies, however, did not demonstrate any marked improvement in liver biomarkers after liraglutide treatment, or the improvements were not sustained ( 19 – 21 , 23 ). Two years of treatment with semaglutide significantly reduced ALT and hs-CRP levels in patients with obesity and/or type 2 diabetes, although significance was lost after adjustment for changes in body weight ( 24 ).…”

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

“…Treatment with GLP-1 receptor monoagonists may also improve liver biomarkers (19). Liraglutide, semaglutide, and exenatide treatment all improved liver biomarkers (19)(20)(21)(22), and liraglutide decreased histological inflammation in patients with biopsy-proven NASH (23). Some studies, however, did not demonstrate any marked improvement in liver biomarkers after liraglutide treatment, or the improvements were not sustained (19)(20)(21)23).…”

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confidence: 99%

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Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study

et al. 2021

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Cotadutide, a dual GLP-1 and glucagon receptor agonist, is under development for nonalcoholic steatohepatitis (NASH) and chronic kidney disease with type 2 diabetes. The effects of cotadutide on hepatic and metabolic parameters were evaluated in participants with overweight/obesity and type 2 diabetes. RESEARCH DESIGN AND METHODSIn this phase 2b study, 834 adults with BMI $25 kg/m 2 and type 2 diabetes inadequately controlled with metformin (glycated hemoglobin A 1c [HbA 1c ]of 7.0%-10.5% [53-91 mmol/mol]) were randomized to double-blind cotadutide 100 μg(n = 100), 200 μg(n =256), or 300 μg(n = 256); placebo (n = 110); or open-label liraglutide 1.8 mg (n = 110)-all administered subcutaneously. Coprimary end points were changes in HbA 1c and body weight at week 14. The originally randomized interventions were continued to week 54. Liver damage biomarkers and liver fibrosis algorithms were assessed. RESULTSCotadutide significantly decreased HbA 1c and body weight at weeks 14 and 54 versus placebo (all P < 0.001). Improvements in lipid profile, AST and ALT levels, propeptide of type III collagen level, fibrosis-4 index, and nonalcoholic fatty liver disease fibrosis score were observed with cotadutide 300 μg versus placebo, but not with liraglutide. Weight loss with cotadutide 200 μg was similar to that with liraglutide 1.8 mg and greater with cotadutide 300 μg versus liraglutide 1.8 mg. The most common adverse events with cotadutide (nausea, 35%; vomiting, 17%) decreased over time. CONCLUSIONSCotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH.Approximately 70% of people with type 2 diabetes, and 93% of people with severe obesity who are candidates for weight reduction procedures or surgeries, have

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Section: Introductionmentioning

confidence: 99%

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Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study

et al. 2021

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“…Glucagon-like peptide-1 (GLP-1) is an important incretin and its receptor GLP-1R is widely distributed in tissues such as liver, pancreas, brain, heart and intestine. GLP-1 can increase liver fatty acid oxidation and insulin sensitivity by binding to GLP-1R, thereby improving NAFLD ( Areti et al, 2020 ). Short-chain fatty acids (SCFA), a metabolic product of the gut microbiota , can regulate the secretion of GLP-1 ( Bayer et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Chlorogenic Acid Improves NAFLD by Regulating gut Microbiota and GLP-1

Shi

Zheng

et al. 2021

Front. Pharmacol.

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Our previous studies have shown that chlorogenic acid (CGA) could significantly improve acute and chronic liver injury through antioxidant and anti-inflammatory activities. However, its effect on non-alcoholic fatty liver disease (NAFLD) are not entirely clear. This study aims to explore the effect of CGA on NAFLD induced by high-fat diet (HFD) and whether it regulates the gut microbiota and Glucagon-like peptide-1 (GLP-1). NAFLD mice were established by HFD and treated with or without CGA. Serum transaminase, fasting blood glucose (FBG), blood lipids, insulin, GLP-1 and lipopolysaccharide (LPS) were detected. Liver histology was evaluated with Hematoxylin-eosin staining. Toll like receptor 4 (TLR4) signaling pathway was analyzed with western blot and inflammatory cytokines were detected with real-time PCR. The content of gut microbiota were determined with real-time PCR of the bacterial 16S rRNA gene. Expressions of intestine tight junctional protein were examined with immunohistochemistry. CGA could alleviate HFD-induced hepatic steatosis and inflammation, reduce serum transaminase, FBG and blood lipids, increase insulin sensitivity. CGA also could reverse HFD-induced activation of TLR4 signaling pathway and expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver. Meanwhile, CGA increased the content of Bifidobacterium and reduced the content of Escherichia coli in feces. Furthermore, CGA could increase the expression of tight junction proteins Occludin and zonula occludens-1 (ZO-1) in intestinal tissue. Moreover, CGA could the level of LPS and increased the level of GLP-1 in portal vein. These results indicated that CGA protected against HFD-induced hepatic steatosis and inflammation probably through its anti-inflammatory effects associated with regulation of gut microbiota and an increase of GLP-1 secretion and thus could be used as a potential drug for prevention and treatment of NAFLD.

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“…Moreover, when compared to dulaglutide, it shows better glucose control and weight reduction in diabetic patients. The authors of the review concluded that GLP-1RA might be a promising treatment for NAFLD patients; however, further studies are needed to confirm this correlation [ 236 ]. Teshome et al also verified the efficacy of GLP-1RA in NAFLD treatment; however, only studies using liraglutide and exenatide were included in this review paper.…”

Section: Incretin Based Therapy For Obesity-related Metabolic Disomentioning

confidence: 99%

Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective

2021

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The prevalence of obesity continues to grow rapidly worldwide, posing many public health challenges of the 21st century. Obese subjects are at major risk for serious diet-related noncommunicable diseases, including type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Understanding the mechanisms underlying obesity pathogenesis is needed for the development of effective treatment strategies. Dysregulation of incretin secretion and actions has been observed in obesity and related metabolic disorders; therefore, incretin-based therapies have been developed to provide new therapeutic options. Incretin mimetics present glucose-lowering properties, together with a reduction of appetite and food intake, resulting in weight loss. In this review, we describe the physiology of two known incretins—glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and their role in obesity and related cardiometabolic disorders. We also focus on the available and incoming incretin-based medications that can be used in the treatment of the above-mentioned conditions.

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Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

Cited by 25 publications

References 64 publications

Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study

Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study

Chlorogenic Acid Improves NAFLD by Regulating gut Microbiota and GLP-1

Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective

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