Lancet paper suggests zabopegdutide may act directly on the liver, offering a fresh angle in the race to tackle MASH.
One idea that dominated the treatment of metabolic liver disease is this: lose weight, and the liver will follow. However, new data from South Korea-based D&D Pharmatech suggests the story may be more complicated and potentially more promising.
The clinical-stage biotech has announced the publication of 12-week Phase 2 data for its investigational therapy, zabopegdutide (DD01), in The Lancet Gastroenterology & Hepatology. The findings show that patients experienced measurable improvements in liver health long before they had lost significant amounts of weight, raising the possibility that the drug may be working directly on the liver itself [1].
The publication builds on the company’s recently announced 48-week biopsy data, which showed statistically significant improvements in both liver scarring (fibrosis) and MASH resolution. The newly published analysis helps explain how those longer-term results may have developed, revealing that meaningful changes were already underway just three months into treatment.
More than a weight-loss story
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis (MASH), have become increasingly common alongside rising rates of obesity and type 2 diabetes. Left unchecked, the condition can progress to liver failure, cirrhosis and liver cancer, yet treatment options remain limited.
Many of today’s therapies improve liver health indirectly by helping patients lose weight. D&D Pharmatech believes zabopegdutide could offer something different.
In the 12-week study, nearly three-quarters of patients receiving the drug reduced liver fat by more than 50%, while almost half reached liver fat levels considered normal. Researchers also saw improvements in markers linked to liver stiffness and fibrosis – signs that the liver was becoming healthier even before dramatic weight loss had occurred.
Among patients who had lost less than 5% of their body weight by Week 12, the therapy still produced significant improvements in liver fat and liver stiffness. Those who lost more weight generally saw even greater benefits, suggesting the treatment may deliver a dual effect: helping the liver directly while also amplifying improvements through weight reduction.
That distinction could prove important as the field looks beyond weight loss alone as the defining measure of success.
Building momentum from earlier findings
The latest publication follows D&D Pharmatech’s announcement that after 48 weeks, patients receiving zabopegdutide achieved statistically significant improvements in both MASH resolution and fibrosis in biopsy-confirmed disease.
“Our recently announced 48-week biopsy results established that zabopegdutide produces clinically meaningful histological improvements in patients with MASH,” said Dr Seulki Lee, President and CEO of D&D Pharmatech. “The publication in the Lancet Gastroenterology & Hepatology demonstrates that these outcomes were foreshadowed by rapid and substantial improvements in liver health within the first 12 weeks of treatment. Importantly, many of these benefits occurred before meaningful weight loss, suggesting that zabopegdutide provides direct therapeutic effects on the liver beyond weight reduction. Together, these findings highlight the differentiated profile of zabopegdutide and support its potential to become a best-in-class therapy for MASH.”
The company says the once-weekly therapy was generally well tolerated and required only a short two-week dose-escalation period before patients reached the target dose.
A crowded field looking for differentiation
The race to develop effective treatments for MASH has accelerated dramatically over the past few years, with several companies pursuing therapies aimed at reducing liver fat, inflammation and fibrosis. As competition intensifies, the question is no longer simply whether a drug works, but how it works – and which patients may benefit most.
If future studies continue to show that zabopegdutide improves liver health independently of major weight loss, it could distinguish itself in an increasingly competitive market. That would be particularly relevant for patients who struggle to achieve substantial weight reduction or whose liver disease continues to progress despite modest weight loss.
“Our 48-week results demonstrated clinically meaningful fibrosis improvement and MASH resolution using the gold-standard biopsy endpoints,” added Lee. “This publication provides important mechanistic evidence showing that those long-term outcomes were preceded by rapid, objective improvements in non-invasive measures of liver disease. We believe these findings further differentiate zabopegdutide from existing therapies and strengthen its potential as a next-generation treatment for patients with MASH. We look forward to advancing the program into late-stage clinical development.”
Why longevity is paying attention
The growing burden of metabolic disease has made liver health an increasingly important part of the longevity conversation. MASLD is closely intertwined with obesity, insulin resistance and cardiovascular disease – conditions that collectively shape not only lifespan but healthspan.
That is why researchers are paying close attention to therapies that can intervene earlier, before irreversible liver damage occurs. While zabopegdutide still has further clinical milestones ahead, the newly published data adds another piece to a rapidly evolving picture: future longevity medicine may need to protect organs directly, rather than relying solely on weight loss as a proxy for better health.
For investors and the broader longevity sector, the findings underscore how the next generation of metabolic therapies is increasingly being judged not just by pounds lost, but by the biological changes happening beneath the surface.
