Abdelgani et al. (1) conducted a randomized clinical trial to examine the efficacy of empagliflozin (EMPA) on hepatic fat content (HFC) reduction in participants with and without diabetes. We read the study with great interest and have a few concerns about it.
First, the presence of attrition bias would compromise the robustness and reliability of the results. The substantial dropout rates, reaching 17% and 25% in each group, pose a substantial challenge. Of note, their precise number of dropouts due to weight limit is unclear. Obesity, which significantly affects metabolic dysfunction–associated fatty liver disease development and prognosis (2), may have been unintentionally excluded, which would have affected the outcomes. Therefore, it is crucial to reveal the exact attrition rate due to obesity.
Second, the existence of selection bias also obscures the clarity of the study. Despite the authors’ assertion of random assignment of participants to either the EMPA or placebo group, the study lacked a detailed explanation regarding the random sequence generation and allocation concealment. Providing such information would enhance the study’s credibility (3).
Finally, EMPA may reduce liver fat content through mechanisms other than weight loss and improved insulin sensitivity. For instance, EMPA may exert a direct action on liver fat. A previous randomized controlled trial revealed that sodium–glucose cotransporter 2 (SGLT2) inhibitors increased plasma free fatty acid (FFA) concentrations (4), leading to an elevation in total body fatty acid oxidation (FAO) (5). The current study also showed a correlation between EMPA-induced plasma FFA increase and HFC reduction. However, based on multivariate regression analysis results, the authors of the current study refuted the direct correlation between plasma FFA concentrations and the reduction of HFC. Nonetheless, the sample size of 38 was insufficient for a robust evaluation of the 16 independent variables, raising the possibility of a type II error. Consequently, future studies with adequate sample sizes should reevaluate EMPA’s effect on FAO, considering other factors like glucagon and ketone bodies.
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Acknowledgments. During the course of preparing this work, the authors used Microsoft Copilot for the purpose of refining their English text for accurate and natural language translations. Following the use of this tool, the authors formally reviewed the content for its accuracy and edited it as necessary. The authors take full responsibility for all the content of this publication.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Handling Editors. The journal editor responsible for overseeing the review of the manuscript was Steven E. Kahn.
