Quantitative effects of sodium-glucose cotransporter-2 inhibitors on liver functions in patients with nonalcoholic fatty liver disease

ABSTRACTBackground The present study aimed to explore the quantitative effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on liver functions in patients with nonalcoholic fatty liver disease (NAFLD).Research design and methods A total of 4771 patients with NAFLD were included for analysis by means of nonlinear mixed effect modeling, where the change rates of liver functions were taken as the evaluation indexes so as to eliminate the potential baseline effects.Results For ALT and AST, the Emax of SGLT-2 inhibitors was −17.8% and −13.9%, respectively, and the ET50 was 6.86 weeks and 10 weeks, respectively. Furthermore, the duration time to achieve 25%, 50%, 75%, and 80% Emax were 2.3 weeks, 6.86 weeks, 20.6 weeks, 27.5 weeks in ALT, 3.4 weeks, 10 weeks, 30 weeks, 40 weeks in AST, respectively. Thus, to realize the plateau period (80% of Emax) of SGLT-2 inhibitors on ALT and AST in patients with NAFLD, 100 mg/day canagliflozin (or 10 mg/day dapagliflozin or 10 mg/day empagliflozin) needs to be taken for 20.6 weeks and 30 weeks, respectively.Conclusions The present study explored the quantitative effects of SGLT-2 inhibitors on liver functions and recommends a therapeutic regimen in patients with NAFLD.KEYWORDS: Quantitative effectssodium-glucose cotransporter-2 inhibitorsliver functionsnonalcoholic fatty liver diseasetherapeutic regimen recommendation Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Authors contributionsConception and design: S He, C Zhang, D Wang; Collection of data: X Chen, C Xu, K Hu, Y Yang, Y Zhang, H Shi, Q Gu; Data analysis and interpretation: X Chen and D Wang; Manuscript writing: X Chen; Final approval of manuscript: All authors.Supplemental dataSupplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2023.2256224.Additional informationFundingThis paper was funded by The Xuzhou Special fund for promoting scientific and technological innovation (No. KC21257), the Initializing Fund of Xuzhou Medical University (No. RC20552111, No. RC20552222), The Fusion Innovation Project of Xuzhou Medical University (No. XYRHCX2021011, No. XYRHCX2022005), the Changzhou Science and Technology Project (No. CJ20229030), Jiangsu Province Education Science Planning Project (No. C/2022/01/36) and the Xuzhou Medical University Labor Education Special Project (No. X1d202209).