A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL

Abstract

Background and aim

Vitamin E is widely prescribed for non-alcoholic steatohepatitis (NASH). Saroglitazar, a novel dual peroxisome proliferator-activator receptor ɑ/γ agonist, is approved in India for non-alcoholic fatty liver disease (NAFLD). No head-to-head comparative study for vitamin E and saroglitazar is available. We studied the efficacy and safety of saroglitazar and vitamin E in NAFLD/NASH.

Materials and methods

We prospectively randomised 175 NAFLD patients into four arms as Saroglitazar 4 mg daily alone (n = 44), vitamin E 800IU daily alone (n = 41), vitamin E and saroglitazar combination (n = 47), and control arm (n = 43). All the baseline variables including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were recorded. Reassessment was done after 24 weeks of treatment.

Results

The mean age and body mass index was 45 ± 11 years and 26 ± 3.6 kg/m², respectively. Compared to control, the decrease in alanine amino transferase levels with saroglitazar, vitamin E, and combination therapy was significant (95% confidence interval [CI]: 6.27–28.25, P = 0.002, 95% CI: −3.39 to 18.88, P = 0.047 and 95% CI: 8.10–29.54, P = 0.001, respectively). The reduction in CAP was significant with saroglitazar and combination therapy (95% CI: −31.94 to 11.99, P = 0.015 and 95% CI: −10.48 to 30.51, P = 0.026, respectively). Only combination therapy shows significant reduction in LSM (95% CI: 0.41–1.68, P = 0.001). Among glycaemic parameters, both saroglitazar alone and combination therapy significantly improved glycosylated haemoglobin levels (P = 0.001 and P = 0.015, respectively), and only combination therapy significantly improved homoeostasis model assessment–estimated insulin resistance (P = 0.047). Saroglitazar alone showed significant reduction in triglyceride and low-density lipoprotein levels (P = 0.038 and P = 0.018, respectively), and combination therapy showed significant increase in high-density lipoprotein levels (P = 0.024).

Conclusions

Combination of Saroglitazar and vitamin E showed statistically significant reduction of LSM and CAP along with biochemical, glycaemic, and lipid parameters.

Clinical trial registry India no

CTRI/2022/01/039538.