scholarly journals Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 73
Author(s):  
Alessandro Mantovani ◽  
Graziana Petracca ◽  
Giorgia Beatrice ◽  
Alessandro Csermely ◽  
Amedeo Lonardo ◽  
...  

To assess the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for treatment of nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH), we performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Three large electronic databases were systematically searched (up to 15 December 2020) to identify placebo-controlled or active-controlled RCTs using different GLP-1 RAs. We included eleven placebo-controlled or active-controlled phase-2 RCTs (involving a total of 936 middle-aged individuals) that used liraglutide (n = 6 RCTs), exenatide (n = 3 RCTs), dulaglutide (n = 1 RCT) or semaglutide (n = 1 RCT) to specifically treat NAFLD or NASH, detected by liver biopsy (n = 2 RCTs) or imaging techniques (n = 9 RCTs). Compared to placebo or reference therapy, treatment with GLP-1 RAs for a median of 26 weeks was associated with significant reductions in the absolute percentage of liver fat content on magnetic resonance-based techniques (pooled weighted mean difference: −3.92%, 95% confidence intervals (CI) −6.27% to −1.56%) and serum liver enzyme levels, as well as with greater histological resolution of NASH without worsening of liver fibrosis (pooled random-effects odds ratio 4.06, 95% CI 2.52–6.55; for liraglutide and semaglutide only). In conclusion, treatment with GLP-1 RAs (mostly liraglutide and semaglutide) is a promising treatment option for NAFLD or NASH that warrants further investigation.

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoyun Wei ◽  
Chunyan Wang ◽  
Shijun Hao ◽  
Haiyan Song ◽  
Lili Yang

Aim. To assess the efficacy of berberine in the treatment of nonalcoholic fatty liver disease through meta-analysis.Method. We searched Embase, Pubmed, Cochrane Library, and so forth, until March 2016 for randomized controlled trials using berberine to treat NAFLD.Result. Six randomized controlled trials involving 501 patients were included in this study. The results showed that the efficacy of reducing TC, LDL, ALT, 2hPG, and HbA1c in NAFLD patients of the berberine group were significantly higher than that of control group. The subgroup analyses on TG, AST, and FBG indicated that treatment combined with berberine decreased TG level in NAFLD patients significantly. Compared with other drugs, berberine alone decreased TG level in NAFLD patients significantly. We also conducted a descriptive analysis on insulin resistance and radiography results that berberine can improve NAFLD patients’ insulin resistance and fatty liver.Conclusion. According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, liver function, insulin resistance, and fatty liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.


Nutrition ◽  
2015 ◽  
Vol 31 (7-8) ◽  
pp. 923-930 ◽  
Author(s):  
Ken Sato ◽  
Masahiko Gosho ◽  
Takaya Yamamoto ◽  
Yuji Kobayashi ◽  
Norimitsu Ishii ◽  
...  

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Alessandro Mantovani ◽  
Graziana Petracca ◽  
Alessandro Csermely ◽  
Giorgia Beatrice ◽  
Giovanni Targher

Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three electronic databases (up to 31 October 2020) for identifying placebo-controlled or head-to-head RCTs that used SGLT-2 inhibitors for treatment of NAFLD. No published RCTs with paired liver biopsy data were available for the meta-analysis. Primary outcome measures were changes in serum liver enzyme levels and liver fat content on imaging techniques. Overall, we included a total of twelve RCTs testing the efficacy of dapagliflozin (n = six RCTs), empagliflozin (n = three RCTs), ipragliflozin (n = two RCTs) or canagliflozin (n = one RCT) to specifically treat NAFLD for a median period of 24 weeks with aggregate data on 850 middle-aged overweight or obese individuals with NAFLD (90% with type 2 diabetes). Compared to placebo/reference therapy, treatment with SGLT-2 inhibitors significantly decreased serum alanine aminotransferase (weighted mean differences (WMD): −10.0 IU/L, 95%CI −12.2 to −7.79 IU/L; I2 = 10.5%) and gamma-glutamyltransferase levels (WMD: −14.49 IU/L, 95%CI −19.35 to −9.63 IU/L, I2 = 38.7%), as well as the absolute percentage of liver fat content on magnetic resonance-based techniques (WMD: −2.05%, 95%CI −2.61 to −1.48%; I2 = 0%). In conclusion, SGLT-2 inhibitors seem to be a promising treatment option for NAFLD.


2021 ◽  
Author(s):  
Samit Ghosal ◽  
Debasis Datta ◽  
Binayak Sinha

Abstract Introduction: Treatment options for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), two conditions which coexist, are limited though weight loss is an important strategy to improve outcomes in either disease. Glucagon-like peptide 1 receptor agonist (GLP1-RA) present a novel option to treat this dual disease by their salutary effects on glycaemic control and weight reduction.Methods: Eight randomized controlled trials on T2D and NAFLD from the Cochrane Library, Embase, and PubMed were included in this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size.Result: In a pooled population of 615 patients—297 on GLP1-RA and 318 in the control arm, GLP1-RA produced a significant improvement in alanine aminotransferase [standardised mean difference (SDM), -0.56, 95%CI, - 0.88 to -0.25, P<0.01], aspartate aminotransferase (SDM, -0.44, SE, 95%CI, -0.64 to -0.24, P<0.01), gamma glutaryl transaminase (SDM, -0.59, 95%CI, -0.86 to -0.34, P<0.01) and reduction in liver fat content (LFC) (SDM, -0.43, 95%CI, - 0.74 to -0.13, P<0.01), as well as glycosylated haemoglobin (SDM, -0.40, 95% CI, -0.61 to -0.19, P<0.01) and weight (SDM, -0.66, 95% CI, -0.88 to -0.45, P<0.01), in comparison to standard of care or placebo. Significant improvement in biopsy resolution was also seen in the GLP1-RA arm (Rate Ratio, 6.59, 95%CI, 2.67 to 16.29, P<0.01). Conclusion: This is possibly the first meta-analysis conducted exclusively in patients with T2D and NAFLD which presents a strong signal that GLP1-RA, improve liver function and histology by improving glycaemia, reducie body weight and hepatic fat, which in turn reduces hepatic inflammation.Trial Registration: PROSPERO (ID: CRD42021228824)


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samit Ghosal ◽  
Debasis Datta ◽  
Binayak Sinha

AbstractTreatment options for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), two conditions which coexist, are limited though weight loss is an important strategy to improve outcomes in either disease. Glucagon-like peptide 1 receptor agonist (GLP1-RA) present a novel option to treat this dual disease by their salutary effects on glycaemic control and weight reduction. Eight randomized controlled trials on T2D and NAFLD from the Cochrane Library, Embase, and PubMed were included in this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size. In a pooled population of 615 patients—297 on GLP1-RA and 318 in the control arm, GLP1-RA produced a significant improvement in alanine aminotransferase [standardised mean difference (SDM), − 0.56, 95% CI − 0.88 to − 0.25, P < 0.01], aspartate aminotransferase (SDM, − 0.44, SE, 95% CI − 0.64 to − 0.24, P < 0.01), gamma glutaryl transaminase (SDM, − 0.60, 95% CI − 0.86 to − 0.34, P < 0.01) and reduction in liver fat content (LFC) (SDM, − 0.43, 95% CI − 0.74 to − 0.12, P < 0.01), as well as glycosylated haemoglobin (SDM, − 0.40, 95% CI, − 0.61 to − 0.19, P < 0.01) and weight (SDM, − 0.66, 95% CI, − 0.88 to − 0.44, P < 0.01), in comparison to standard of care or placebo. Significant improvement in biopsy resolution was also seen in the GLP1-RA arm (Rate Ratio, 6.60, 95% CI 2.67 to 16.29, P < 0.01). This is possibly the first meta-analysis conducted exclusively in patients with T2D and NAFLD which presents a strong signal that GLP1-RA, improve liver function and histology by improving glycaemia, reducing body weight and hepatic fat, which in turn reduces hepatic inflammation.Trial Registration: PROSPERO (ID: CRD42021228824).


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