Dapagliflozin benefits liver disease patients

The type 2 diabetes treatment dapagliflozin appears to also benefit patients with liver disease, researcher reported on June 4, 2025 in The BMJ today.

The findings suggest that treatment with dapagliflozin, compared with placebo, improved metabolic dysfunction-associated steatohepatitis (MASH). MASH happens when excess fat accumulates in the liver, causing inflammation and liver fibrosis.

“Dapagliflozin for 48 weeks can lead to MASH improvement without worsening of fibrosis, MASH resolution without worsening of fibrosis, and fibrosis improvement without worsening of MASH, in patients with MASH,” said the investigators. “These results support the potential for dapagliflozin to provide benefit to patients with biopsy diagnosed MASH and liver fibrosis.” they added.

As background, the authors noted that prior studies have indicated that SGLT-2 inhibitors, like dapagliflozin, can improve liver fat content, liver enzymes, and liver stiffness. But this is the first study on the specific efficacy of dapaglifloxin for treating MASH.

The randomized, placebo-controlled trial took place at six hospitals in China. The researchers enrolled 154 adults with biopsy-diagnosed MASH, with or without type 2 diabetes.

Almost half (45%) of the subjects had type 2 diabetes, and almost all had liver fibrosis (33% stage 1, 45% stage 2, 19% stage 3).

All subjects were randomized to receive daily 10 mg of oral dapagliflozin or a matching placebo for 48 weeks.

The primary endpoint was MASH improvement, defined as a decrease of at least 2 points in nonalcoholic fatty liver disease activity score (NAS), or a NAS of ≤3 points) without worsening of liver fibrosis, defined as no increase of fibrosis stage, at 48 weeks.

At endpoint, the investigators reported MASH improvement without worsening of fibrosis appeared in 53% (41/78) of the subjects in the dapagliflozin group and 30% (23/76) in the placebo group, a significant difference (P=0.006). Mean difference of NAS was −1.39, a significant difference (P<0.001).

They reported that resolution of MASH without worsening of fibrosis occurred in 23% (18 of 78) the subjects in the dapagliflozin group compared with 8% (6 of 76) in the placebo group, a significant difference (P=0.01).

They also reported fibrosis improvement without worsening of MASH in 45% (35 of 78) of the subjects in the dapagliflozin group compared with 20% (15 of 76) in the placebo group, a significant difference (P=0.001).

The percentage of subjects who discontinued treatment due to adverse events was 1% (1 of 78) in the dapagliflozin group and 3% (2 of 76) in the placebo group.

The authors concluded, “Our findings indicate that dapagliflozin may affect key aspects of MASH by improving both steatohepatitis and fibrosis.”

“Large scale and long-term trials are needed to further confirm these effects,” they added.