Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis.

Background And Aims: No meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD).

Methods: Electronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events.

Results: Data from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: -5.41 to -2.36); P < 0.01; I = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: -3.26 to -3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to -6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to -1.23); P = 0.04; I = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: -8.45 to -2.61); P < 0.01; I = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: -5.87 to -1.23); P < 0.01; I = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: -14.64 to -3.34); P = 0.002; I = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to -0.45); P = 0.002; I = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76-7.06); P = 0.14; I = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69-1.65); P = 0.77; I = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33-4.22); P = 0.003; I = 24%], diarrhea [RR 2.05 (95%CI: 1.17-3.60); P = 0.01; I = 66%], nausea [RR 4.98 (95%CI: 3.23-7.67); P < 0.001; I = 0%] and vomiting [RR 3.90 (95%CI: 1.75-8.68); P < 0.01; I = 54%] were higher with semaglutide.

Conclusion: This meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.