scholarly journals GLP-1 receptor agonists for NAFLD treatment in patients with and without type 2 diabetes: an updated meta-analysis

2020 ◽  
Vol 1 (3) ◽  
pp. 108-123 ◽  
Author(s):  
Alessandro Mantovani ◽  
Giorgia Beatrice ◽  
Graziana Petracca ◽  
Filippo Pampagnin ◽  
Damiano Sandri ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Receptor Agonists ◽  
Promising Treatment ◽  
Glucagon Like Peptide 1 ◽  
Mean Differences

Aim: Recent randomized controlled trials (RCTs) have tested the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) to specifically treat non-alcoholic fatty liver disease (NAFLD). We performed a meta-analysis of RCTs to investigate the efficacy of GLP-1 RAs for treatment of NAFLD or non-alcoholic steatohepatitis (NASH). Methods: We systematically searched PubMed and ClinicalTrials.Gov databases utilizing specific terms to identify placebo-controlled or head-to-head RCTs (last research on March 1, 2020) involving NAFLD patients with the aim to evaluate the efficacy of GLP-1 RAs to treat NAFLD/NASH. Primary outcomes were changes in serum liver enzymes, liver fat content, or histologic resolution of NASH. Weighted mean differences (WMD) were used to test the differences between the treatment arms. Results: Overall, we found 7 placebo-controlled or head-to-head RCTs involving 472 middle-aged individuals (66% men; 77% with established diabetes) followed for a median of 16 weeks that have used liraglutide or exenatide to treat NAFLD on imaging (n = 6) or biopsy (n = 1). Compared to placebo or reference therapy, treatment with GLP-1 RAs decreased serum alanine aminotransferase [n = 7 studies; WMD: -8.77 IU/L, 95% confidence intervals (CI) -17.69 to 0.14 IU/L; I2 = 87.3%] and gamma-glutamyltransferase levels (n = 4 studies; WMD: -10.17 IU/L, 95% CI -14.27 IU/L to -6.07 IU/L; I2 = 0%) and imaging-defined liver fat content (n = 4 studies; WMD: -6.23%, 95% CI -8.95% to -3.51%; I2 = 85.9%). In one RCT involving 55 patients with biopsy-proven NASH, a 48-week treatment with liraglutide also led to a greater histological resolution of NASH than placebo. Conclusions: GLP-1 RAs (mostly liraglutide) seem to be a promising treatment option for NAFLD or NASH.

Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 52 (07) ◽  
pp. 517-526
Author(s):  
Yuhan Zhang ◽  
Tian Cai ◽  
Junyu Zhao ◽  
Congcong Guo ◽  
Jinming Yao ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease. However, the treatment is limited. The aim of this meta-analysis was to evaluate the effects and safety of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4 (DPP-4I), in treating NAFLD. Studies were sourced from electronic databases including PubMed, CENTRAL (Cochrane Controlled Trials Register), Embase, Medline, Web of Science, Clinical Trials, and CNKI to identify all randomized controlled clinical trials (RCTs) and non-RCTs in adult patients with NAFLD. Key outcomes were changes in serum levels of liver enzymes and improvement in hepatic histology and fat content measured by imaging or liver biopsy. Stata14.0 and RevMan5.3 were used for the meta-analysis. Seven studies with 269 NAFLD patients were included. Compared to the control group, sitagliptin treatment improved serum gamma-glutamyl transpeptidase (GGT) levels in the RCT subgroup (SMD = 0.79, 95% CI: 0.01–1.58). However, there was no significant improvement in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels following sitagliptin treatment. Four of the included studies performed liver imaging, but sitagliptin treatment did not result in a significant reduction in liver fat content. Only five participants developed sitagliptin-related gastrointestinal discomfort. Our study suggests that sitagliptin effects individuals with NAFLD by improving serum GGT. Although sitagliptin is safe and well tolerated in NAFLD patients, it exerts no beneficial effects on liver transaminase and liver fat content in these patients.

scholarly journals Effects of a multifactorial ecosustainable isocaloric diet on liver fat in patients with type 2 diabetes: randomized clinical trial

2020 ◽  
Vol 8 (1) ◽  
pp. e001342 ◽  
Author(s):  
Giuseppe Della Pepa ◽  
Claudia Vetrani ◽  
Valentina Brancato ◽  
Marilena Vitale ◽  
Serena Monti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Significant Difference ◽  
Dietary Components ◽  
Mufa Diet

IntroductionTreatment options for non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) are still a matter of debate. We compared the effects of a diet including different components versus a proven beneficial diet rich in monounsaturated fatty acids (MUFAs) on liver fat in T2D.Research design and methodsAccording to a parallel design, 49 individuals with T2D, overweight/obese, with high waist circumference, 35–75 years-old, in satisfactory blood glucose control with diet or drugs not affecting liver fat content, were randomly assigned to an 8-week isocaloric intervention with a MUFA diet (n=26) or a multifactorial diet rich in fiber, MUFA, n-6 and n-3 polyunsaturated fatty acids, polyphenols, and vitamins D, E, and C (n=23). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS complete data were available for n=21 (MUFA diet) and n=18 (multifactorial diet) participants.ResultsAdherence to dietary interventions was optimal. No significant differences between groups in body weight reduction, plasma glycated hemoglobin, insulin, glucose, lipids and liver enzymes were observed. Liver fat significantly decreased after both the multifactorial diet (9.18%±7.78% vs 5.22%±4.80%, p=0.003) and the MUFA diet (9.47%±8.89% vs 8.07%±8.52%, p=0.027) with a statistically significant difference between changes either in absolute terms (−4.0%±4.5% vs −1.4%±2.7%, p=0.035) or percent (−40%±33% vs −19%±25%, p=0.030).ConclusionsAn isocaloric multifactorial diet including several beneficial dietary components induced a clinically relevant reduction of liver fat in patients with T2D, more pronounced than that induced by simply replacing saturated fat with MUFA. This suggests that the ‘optimal diet’ for NAFLD treatment in T2D should be based on synergic actions of different dietary components on multiple pathophysiological pathways.Trial registration numberNCT03380416.

Liver Fat Content in People with Pituitary Diseases: Influence of Serum IGF1 Levels

2017 ◽  
Vol 50 (04) ◽  
pp. 303-307 ◽  
Author(s):  
Amandine Nguyen ◽  
Fréderic Ricolfi ◽  
Brivel Lemogne ◽  
Serge Aho ◽  
Stéphanie Lemaire ◽  
...  
Keyword(s):  
Fat Content ◽  
Liver Fat ◽  
Healthy Controls ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Predictive Variables ◽  
Pituitary Diseases ◽  
And Gender ◽  
The Relationship

AbstractNon-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome, and type 2 diabetes. NAFLD is also seen in patients with endocrinopathies. However, the relationship between endocrine diseases and the development of NAFLD is not well known. In this study, we set out to determine whether liver fat content (LFC) was associated with IGF1 levels in people with pituitary diseases (PD). Eighty-nine patients with pituitary diseases and 74 healthy controls were included in this study. LFC was measured using MRI. Hepatic steatosis was defined as LFC>5.5%. Patients with PD were older, and had a higher BMI than healthy controls. LFC was significantly higher in people with PD than in controls (6.5% vs. 3.2%; p<0.001). LFC was negatively associated with the IGF1 level. The prevalence of steatosis was higher in PD patients than in controls (36.3% vs. 14.8%; p=0.002). In multivariate analysis, which included patients and controls, the predictive variables for steatosis were age, BMI and IGF1 levels, whereas the presence of pituitary diseases and gender were not associated with steatosis. Our data showed that LFC was strongly associated with IGF1 levels. These results suggest that steatosis associated with PD is probably a consequence of a low IGF1 level in these patients.

Diabetes Remission Clinical Trial (DiRECT)—Plasma Liver Function Tests Reflect Change in Liver Fat Content in Early Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1834-P
Author(s):  
SVIATLANA V. ZHYZHNEUSKAYA ◽  
AHMAD AL-MRABEH ◽  
CARL PETERS ◽  
ALISON C. BARNES ◽  
KIEREN G. HOLLINGSWORTH ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Liver Function ◽  
Liver Function Tests ◽  
Fat Content ◽  
Diabetes Remission ◽  
Liver Fat ◽  
Early Type ◽  
Liver Fat Content

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

2006 ◽  
Vol 291 (2) ◽  
pp. E282-E290 ◽  
Author(s):  
Riikka Lautamäki ◽  
Ronald Borra ◽  
Patricia Iozzo ◽  
Markku Komu ◽  
Terho Lehtimäki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Liver Steatosis ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Artery Disease ◽  
Myocardial Insulin Resistance ◽  
High Liver

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

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