Reply: Aspirin and GLP-1RAs—The missing confounders of empagliflozin for MASLD without diabetes mellitus?

We thank Hu et al1 for their letter commenting on our recent article "Effect of empagliflozin on liver fat in metabolic-dysfunction associated steatotic liver disease patients without diabetes mellitus: A randomized, double-blind, placebo-controlled trial."2 They commented that aspirin3 and glucagon-like peptide-1 receptor agonists4 may act as confounding factors on the causality of empagliflozin reducing hepatic steatosis in patients with metabolic dysfunction–associated steatotic liver disease without diabetes mellitus. As it was a randomized study, all this information was available, and we reviewed the records of the 98 study participants. There were 11 (11.2%) aspirin users with 5 (10.2%) in the empagliflozin group, and 6 (12.2%) in the control group, with no statistically significant difference between the 2 groups (p = 0.749). There was, however, no glucagon-like peptide-1 receptor agonist user as this study only included patients without diabetes, in which glucagon-like peptide-1 receptor agonist was only approved for this indication locally. However, we did not think subgroup analysis based on aspirin use was meaningful as this study was not powered to explore this. In fact, a properly conducted randomized controlled study would be able to eliminate both measured and unmeasured confounders, including what has been proposed by the authors.1