P15 Comparative efficacy of pioglitazone and saroglitazar in non-alcoholic fatty liver disease: a Bayesian network meta-analysis

Background and Aims

Non-alcoholic fatty liver disease (NAFLD) is considered a part of the metabolic syndrome. Two drugs, saroglitazar (S) and pioglitazone (P) are known to have beneficial effects on the metabolic syndrome. This Bayesian network meta-analysis (NMA) was conducted to compare the relative efficacy of these 2 drugs on NAFLD.

Method

An electronic database search using the Cochrane library yielded 11 randomised prospective study for this NMA. The R version 4.2.3 (64 bit) was used to analyse the data. Selection bias was screened with a funnel plot and publication bias using the Cochrane risk of bias algorithm. The standardized mean difference (SMD) was used as an effect size estimate and Surface Under the Cumulative RAnking curve (SUCRA) value was used to rank S and P in comparison to placebo as the comparator.

Results

This NMA was conducted on a pooled population of 930 patients (379 on P, 159 on S, and 392 on placebo) diagnosed with NAFLD either on liver biopsy or radiologically along with transaminase estimation. S (ALT: SMD -0.94 [95% CI -1.25 to -0.63] and AST: SMD -0.44 [95% CI -0.70 to -0.19]) and P (ALT: SMD -0.4 [95% CI -0.62 to -0.20] and AST: SMD -0.30 [95% CI -0.47 to -0.12]) improved inflammatory markers significantly with S ranking higher than P on SUCRA scoring (ALT: 0.99 with P and 0.50 with P, ALT: 0.89 with S and 0.59 with P). The impact on lobular inflammation was comparable between P (SMD -0.22 [95% CI -0.46 to 0.01]; SUCRA 0.77) and S (SMD -0.12 [95% CI -0.56 to 0.32]; SUCRA 0.51). S (SMD -0.83 [95% CI -1.4 to -0.26]; SUCRA score of 0.90) was superior to P (SMD -0.50 [95% CI -0.87 to -0.12]; SUCRA 0.55) in improvement of hepatic ballooning. However P (SMD -0.70 [95%CI -1.14 to -0.25]; SUCRA 0.92) was superior to S (SMD -0.23 [95% CI -0.59 to 0.14; SUCRA 0.47) in improvement of steatosis(figure 1)

Conclusion

Both S and P have a salutary effect on NAFLD. However P seems to be more efficacious early in the course of the disease reducing steatosis. Once steatosis progresses to inflammation it appears that there is more benefit with use of S than P. However larger and adequately powered randomized controlled trials with these agents need to replicate these findings convincingly, to ensure these drugs can be used in routine clinical practice.