NR1H4 and Insulin resistance: High-exposure insulin resistance was improved by 18.3% in the 25 mg/day group, while the high dose 50 mg/day group was non-significant with a point estimate of 10.8% improvement.608,609 This lack of significance may be due to the small sample size of ~20 patients per group, but if interpreted as is, the trial reveals that OCA-mediated FXR agonism provides dose-dependent outcomes, where overshooting target agonist efficacy gives less favorable or potentially negative outcomes.