Dapagliflozin shows promise in progressive liver disease

Diabetes drug dapagliflozin could also be beneficial for patients with progressive liver disease, a clinical trial has shown.

A clinical trial of 154 adults with fatty liver disease or metabolic dysfunction-associated steatohepatitis (MASH) found a significant disease improvement in those taking the sodium-glucose cotransporter 2 inhibitor compared with placebo.

It follows several studies reporting that SGLT-2 inhibitors can improve liver fat content, liver enzymes, and liver stiffness, but it is the first trial to test the theory in patients with MASH.

Reporting in the BMJ, the Chinese researchers randomly assigned participants to receive 10 mg of dapagliflozin or matching placebo once daily for 48 weeks and health education sessions twice a year. 

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

After 48 weeks, 53% (41 of 78) participants in the dapagliflozin group showed improvement in MASH as shown by liver biopsy without worsening of fibrosis compared with 30% (23 of 76) in the placebo group. 

Improvement was defined as a decrease of at least 2 points in individual’s non-alcoholic fatty liver disease activity score (NAS) or a score of 3 points or less. 

The team also reported resolution of MASH without worsening of fibrosis in 23% (18 of 78) participants in the dapagliflozin group compared with 8% (6 of 76) in those taking placebo.

Fibrosis improvement without worsening of MASH was also reported in 45% (35 of 78) participants in the dapagliflozin group compared with 20% (15 of 76) in the placebo group.

Only three patients discontinued treatment due to side effects, one of whom was taking dapagliflozin.

Those taking part were mainly men with an average age of 35 years, but various analyses done on the results suggest they were robust, they said.

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

A linked editorial pointed out that as more drugs become available, therapeutic decisions will likely become increasingly tailored to individual patient profiles.

‘Ideally, such treatments should provide cardiovascular benefit, have an established safety profile, and be accessible to broad and diverse patient populations,’ it noted.

The British Liver Trust recently warned that mortality rates from liver disease have risen by more than 400% in the past five decades, while deaths from other major illnesses have fallen.

It also found that most ICBs in England do not have effective referral pathways for diagnosing and managing liver disease. 

Two-thirds did not have monitoring of local liver disease health statistics, despite cases soaring.

Professor Philip Newsome, medical advisor to the British Liver Trust, said: ‘This trial investigating dapagliflozin for MASH shows encouraging results, with significant improvements in both MASH resolution and fibrosis compared to placebo. 

‘Although the magnitude of benefit is noteworthy, it is important to recognise that other emerging therapies, such as FGF21 analogues and GLP-1 receptor agonists, have demonstrated even stronger efficacy in resolving MASH and improving fibrosis. 

‘Nonetheless, dapagliflozin could offer a valuable treatment option, particularly in patients with type 2 diabetes, and these results support its potential role as part of a multi-pronged therapeutic approach to MASH management.’