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The effects of GLP-1 receptor agonists on histopathological and secondary biomarkers of non-alcoholic steatohepatitis: A systematic review and meta-analysis

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Petr Borodavkin, William Sheridan, Claudia Coelho, Eduard Ostarijas, Zoulikha M Zair, Alexander D Miras, Barbara McGowan, Carel le Roux, Royce Vincent, Georgios K Dimitriadis

Original languageEnglish
JournalDIABETES OBESITY AND METABOLISM
Accepted/In press27 Sep 2021

King's Authors

Abstract

Aims:
This systematic review aimed to evaluate the efficacy of GLP-1 receptor agonists (RAs) in the management of patients with biopsy proven non-alcoholic steatohepatitis (NASH), focusing on histopathological and secondary biochemical markers.
Materials and methods:
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and SCOPUS were critically appraised for peer-reviewed manuscripts that suitably fulfilled our protocol’s inclusion criteria. Mean Differences (MD), Standardized Mean Differences (SMD), and Risk Ratios (RR) were reported with 95% Confidence Intervals (CI) and derived through a random-effects model from baseline and endpoint readings. We excluded studies investigating NAFLD.
Results:
Out of 2551 studies identified initially, 4 were meta-analysed. Data from 406 NASH patients were included, of which 250 had TD2M and 243 were female. GLP-1RA were found to be more effective in improving NASH (RR= 2.67, 95% CI= [1.87; 3.81]) and fibrosis (RR= 1.29, 95% CI= [0.99; 1.70]) compared to placebo as well as each individual parameter of NAFLD Activity Score (NAS) system. GLP-1RAs also elicited improvements from baseline scores for metabolic (HbA1c, FPG, and BMI) and secondary biomarkers of NASH (ALT, AST, GGT, and CCCF30). No significant alterations were recorded for the lipid profile (LDL, HDL) and insulin resistance (HOMA-IR). Injectable semaglutide (0.4mg/day) exhibited the most significant improvements on key histopathological and secondary biomarkers of NASH.
Conclusions:
This systematic review validated previous evidence of beneficial histological effects of GLP-1RAs on NASH. It also highlighted the need for further research to fully elucidate the optimal GLP-1RA dose regimen and treatment length on NASH histopathological and biochemical markers.

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