Dapagliflozin Improves MASH Without worsening liver fibrosis in new Trial
Researchers have found in a randomized trial in China that dapagliflozin, an SGLT2 inhibitor, improved metabolic dysfunction-associated steatohepatitis (MASH) without worsening liver fibrosis.
The study population included younger, predominantly male patients with lower BMI and less advanced disease, highlighting potential for broader MASH treatment options beyond the single FDA-approved therapy.
A study was done to assess the efficacy and safety of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in participants with metabolic dysfunction-associated steatohepatitis (MASH). All participants were randomly assigned to receive 10 mg orally of dapagliflozin or matching placebo once daily for 48 weeks.
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.
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.
Reference:
BMJ 2025; 389 doi: https://doi.org/10.1136/bmj-2024-083735 (Published 04 June 2025)
