Background and aims: We investigated whether empagliflozin reduces hepatic steatosis in metabolic-dysfunction associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM).
Approach and results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without DM (fasting plasma glucose <7 mmol/L and HbA1c <6.5%) who had magnetic resonance imaging-proton density fat fraction [MRI-PDFF] ≥5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. Primary outcome was difference in change of MRI-PDFF between two groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF <5%), ALT drop≥17U/L, MRI-PDFF decline≥30%, combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age:55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. Empagliflozin group had greater reduction in median MRI-PDFF compared to placebo group (-2.49% vs -1.43%;p=0.025), with a non-significant trend of resolution of hepatic steatosis (44.9% vs 28.6%;p=0.094). There was no significant difference in ALT drop≥17U/L (16.3% vs 12.2%;p=0.564), MRI-PDFF drop≥30% (49.0% vs 40.8%;p=0.417), and composite outcome (8.2% vs 8.2%;p=1.000). Empagliflozin group had greater drop in body weight (-2.7 vs -0.2 kg), waist circumference (-2.0 vs 0 cm), fasting glucose (-0.3 vs 0 mmol/L) and ferritin (-126 vs -22 pmol/L) (all p<0.05).
Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in non-diabetic MASLD subjects. (ClinicalTrials.gov Identifier: NCT04642261).
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