Type 2 diabetes drug shows improvements in patients with progressive liver disease

Type 2 diabetes drug shows improvements in patients with progressive liver disease

The sodium glucose cotransporter 2 (SGLT-2) inhibitor drug dapagliflozin, commonly used to treat type 2 diabetes, also shows improvements in patients with progressive liver disease, finds a clinical trial from China published byThe BMJToday.

The results show that treatment with dapagliflozin improved metabolic dysfunction-associated steatohepatitis (MASH) - a condition in which excess fat builds up in the liver, leading to inflammation and liver fibrosis (a buildup of scar tissue) compared to placebo.

MASH affects more than 5% of adults, more than 30% of people with diabetes or obesity, and can progress to cirrhosis in up to 25% of people.

Several studies have reported that SGLT-2 inhibitors can improve liver fat content, liver enzymes, and liver stiffness, but no study has been conducted in patients with MASH.

To account for this, researchers enrolled 154 adults (median age 35 years; 85% men) diagnosed with MASH after liver biopsy at six medical centers in China from November 2018 to March 2023.

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

After an initial screening biopsy, participants were randomly assigned to receive 10 mg of dapagliflozin or matching placebo once daily for 48 weeks and to attend health education sessions twice a year.

Various factors, including body weight, blood pressure, blood sugar, liver enzymes, physical activity, diet, insulin and lipids, were also assessed at enrollment and throughout the trial.

Improvement in MES was defined as a decrease of at least 2 points in activity score (NAS) or a NAS of 3 points or less.

After a study biopsy at Week 48, 53% (41 of 78) participants in the dapagliflozin group showed improvement in MASH, without fibrosis (defined as no increase in fibrosis stage) versus 30% (23 of 76) in the placebo group.

Resolution of MASH occurred without worsening of fibrosis in 23% (18 of 78) participants in the dapagliflozin group, compared with 8% (6 of 76) in the placebo group.

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

The percentage of participants 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 researchers acknowledge that the study was conducted in a Chinese population, limiting its broader generalizability, and that female and elderly patients were underrepresented. However, they note that the results were consistent after further analysis, suggesting that they are robust.

Therefore, they conclude: “Our results indicate that dapagliflozin may influence important aspects of MASH by improving both steatohepatitis and fibrosis.” Large, long-term trials are needed to further confirm these effects, they add.

The coming years are expected to be particularly exciting in the field of pharmacological treatment of MASH, researchers from Argentina say in a linked editorial.

As more drugs become available, therapeutic decisions are likely to become increasingly tailored to individual patient profiles, they write. “Ideally, such treatments should provide cardiovascular benefit, have an established safety profile, and be accessible to broad and diverse patient populations,” they conclude.

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