New Diabetes Treatment Shows Promise for Liver Disease Management

A recent clinical study has revealed that dapagliflozin, a sodium glucose cotransporter 2 (SGLT-2) inhibitor commonly used in the management of type 2 diabetes, may offer significant benefits for patients suffering from progressive liver disease. The study, conducted in China and published in the British Medical Journal, focused on the effects of dapagliflozin on metabolic dysfunction-associated steatohepatitis (MASH), a condition characterized by fat accumulation in the liver that can lead to inflammation and fibrosis.

MASH is prevalent in over 5% of the adult population, with incidence rates exceeding 30% among individuals with diabetes or obesity. It poses a serious risk, as up to 25% of those affected may progress to cirrhosis. Although previous research has indicated that SGLT-2 inhibitors can positively influence liver fat content and related metrics, this is the first clinical trial specifically targeting patients with MASH.

The research involved 154 adults, predominantly male (85%), with an average age of 35, all of whom had been diagnosed with MASH via liver biopsy at six medical centers in China between November 2018 and March 2023. Notably, nearly half of the participants also had type 2 diabetes, and almost all presented with liver fibrosis.

Participants were randomly assigned to receive either 10 mg of dapagliflozin or a placebo daily for a duration of 48 weeks, alongside health education sessions held biannually. Throughout the trial, various health parameters--including body weight, blood pressure, blood glucose levels, liver enzymes, and dietary habits--were monitored.

Improvement in MASH was defined as a reduction of at least two points in the non-alcoholic fatty liver disease activity score (NAS) or a NAS of three points or lower. At the conclusion of the study, 53% of those receiving dapagliflozin demonstrated improvement in MASH without any worsening of fibrosis, compared to 30% in the placebo group. Furthermore, 23% of participants in the dapagliflozin cohort achieved resolution of MASH without a deterioration in fibrosis, whereas only 8% of the placebo group experienced similar outcomes. Additionally, 45% of patients in the dapagliflozin group showed improvement in fibrosis without worsening MASH, contrasted with 20% in the placebo group.

The treatment was well tolerated, with only 1% of participants in the dapagliflozin group discontinuing due to adverse effects, compared to 3% in the placebo group. The researchers noted limitations in their study, particularly the demographic focus on a Chinese population, which may restrict the applicability of the findings to broader populations. They also highlighted the underrepresentation of female and older patients within the study.

Despite these limitations, the researchers concluded that dapagliflozin appears to positively influence key aspects of MASH, specifically by enhancing both steatohepatitis and fibrosis outcomes. They emphasized the need for large-scale, long-term trials to further validate these findings.

Experts from Argentina, in a related editorial, expressed optimism regarding the future of pharmacological treatments for MASH, suggesting that as more therapeutic options become available, treatment strategies will increasingly be tailored to individual patient needs. They highlighted the importance of ensuring these treatments not only improve liver health but also provide cardiovascular benefits, have established safety profiles, and are accessible to diverse patient groups.