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Gut Microbiota Predicts Treatment Response to Empagliflozin Among MASLD Patients Without Diabetes Mellitus

Ng HY, Zhang L, Tan JT, Hui RWH, Yuen MF, Seto WK, Leung WK, Cheung KS

Liver international : official journal of the International Association for the Study of the Liver, 2025

45 participants

Abstract

BACKGROUND AND AIM: We aimed to investigate whether gut microbiota could predict the treatment response to pharmacological agents among metabolic dysfunction-associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM), as data are lacking.

METHODS: We prospectively followed up non-diabetic MASLD patients who used empagliflozin. Clinical, anthropometric, laboratory assessments and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were performed from baseline to week 52 (EOT). Baseline stool samples were collected, and shotgun DNA metagenomic sequencing was performed to profile microbiome. The primary outcome was treatment response to empagliflozin at EOT, defined as MRI-PDFF decline ≥ 30% at EOT from baseline. Linear discriminant analysis [LDA] effect size was used to identify putative bacterial species. Multivariable logistic regression was used to derive adjusted odds ratio (aOR) of outcome with bacterial species by adjusting for clinical factors.

RESULTS: Twenty-two (48.9%) of 45 patients (median age: 56.9 years [IQR: 51.0-63.2]; male: 23 [51.1%]) achieved treatment response at EOT. There was difference in alpha diversity (Shannon index: p < 0.001; Simpson index: p = 0.001) and beta diversity (p = 0.048) in baseline microbiome between treatment response and non-response groups. Faecalibacterium prausnitzii (log10LDAscore = 4.27), Lachnospira pectinoschiza (log10LDAscore = 3.99), Anaerostipes hadrus (log10LDAscore = 3.98), Roseburia…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 45 participants or records.

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