OBJECTIVE: To assess the efficacy and safety of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in participants with metabolic dysfunction-associated steatohepatitis (MASH).
DESIGN: Multicentre, double blind, randomised, placebo controlled trial.
SETTING: Six tertiary hospitals in China from 23 November 2018 to 28 March 2023.
PARTICIPANTS: 154 adults with biopsy diagnosed MASH, with or without type 2 diabetes.
INTERVENTIONS: All participants were randomly assigned to receive 10 mg orally of dapagliflozin or matching placebo once daily for 48 weeks.
MAIN OUTCOME MEASURES: The primary endpoint was MASH improvement (defined as a decrease of at least 2 points in non-alcoholic fatty liver disease activity score (NAS) or a NAS of =3 points) without worsening of liver fibrosis (defined as without increase of fibrosis stage) at 48 weeks. The secondary endpoints included the MASH resolution without worsening of fibrosis and fibrosis improvement without worsening of MASH. Analyses used the intention-to-treat dataset.
RESULTS: MASH improvement without worsening of fibrosis was reported in 53% (41/78) of participants in the dapagliflozin group and 30% (23/76) in the placebo group (risk ratio 1.73 (95% confidence interval (CI) 1.16 to 2.58); P=0.006). Mean difference of NAS was -1.39 (95% CI -1.99 to -0.79); P<0.001). MASH resolution without worsening of fibrosis occurred in 23% (18/78) of participants in the dapagliflozin group and 8% (6/76) in the placebo group (risk ratio 2.91 (95% CI 1.22 to 6.97); P=0.01). Fibrosis improvement without worsening of MASH was reported in 45% (35/78) of participants in the dapagliflozin group, as compared with 20% (15/76) in the placebo group (risk ratio 2.25 (95% CI 1.35 to 3.75); P=0.001). The percentage of individuals who discontinued treatment because of adverse events was 1% (1/78) in the dapagliflozin group and 3% (2/76) in the placebo group.
CONCLUSION: Treatment with dapagliflozin resulted in a higher proportion of participants with MASH improvement without worsening of fibrosis, as well as MASH resolution without worsening of fibrosis and fibrosis improvement without worsening of MASH, than with placebo.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03723252.
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
| Gastroenterology |  |
The conclusion was that dapagliflozin may improve MASH, but weight loss improves MASH / metabolic parameters. In this placebo-controlled RCT, the treatment group had significantly greater weight loss. Was the improvement in MASH / metabolic parameters then simply due to weight loss, in this case brought about in this instance by dapagliflozin?
A relatively small trial with a predictable result.
This is a double-blind study of 154 people with biopsy proven MASH. It showed that the STLG2 inhibitor dapaglozin was effective in arresting or reversing MASH in 53% of patients versus 30% in the control group. The medication also improved fibrosis scores by the fiber scan test.