The global burden of metabolic dysfunction-associated steatohepatitis (MASH), formerly known as NASH, has reached epidemic proportions. Affecting an estimated 115 million people worldwide, MASH represents the most severe form of nonalcoholic fatty liver disease (NAFLD) and is closely tied to obesity, type 2 diabetes, and cardiovascular disease. Yet despite its prevalence and devastating clinical impact, the therapeutic landscape for it has remained largely barren.
How, however, recent developments in the field signal a long-awaited shift. Novo Nordisk’s $4.7 billion acquisition of Akero Therapeutics, announced earlier this year underscores the strategic value of MASH as a critical frontier in cardiometabolic medicine. Akero’s efruxifermin, a long-acting FGF21 analog, has shown strong phase III results demonstrating histologic improvement and reversal of fibrosis, reaffirming that effective MASH treatment can also improve systemic metabolic health.
This landmark transaction highlights a broader truth: the lines between liver disease, diabetes, and cardiovascular health are disappearing. The next wave of innovation will come from therapies that address metabolic dysfunction as an interconnected system rather than isolated endpoints.
The metabolic continuum
MASH sits at the intersection of multiple metabolic pathways, insulin resistance, lipid metabolism, and inflammatory signaling. Its pathophysiology makes it particularly challenging to treat; traditional single-target drugs often fail to reverse fibrosis or meaningfully alter disease trajectory.
However, recent clinical data suggest that targeting metabolic regulators with broader systemic activity may hold the key. GPR119, a G protein-coupled receptor involved in glucose and lipid homeostasis, has emerged as one such target.
At the 2025 American Association for the Study of Liver Diseases (AASLD) annual meeting, multiple companies presented encouraging data. For example, Rivus’s HU-6, an ANT-channel activator, achieved statistically significant reductions in liver fat content at six months versus placebo, with up to 58 percent of treated patients achieving ≥30 percent liver fat reduction. MetaVia’s vanoglipel, a next-generation GPR119 agonist, also demonstrated clinically meaningful improvements in glucose control, liver health, and plasma lipidomic profiles after just 16 weeks of treatment.
The results presented in a late-breaker oral session for Rivus and a poster for MetaVia reinforce that MASH drug discovery is entering a period of sustained progress. While diverse in mechanism, both programs share a unifying goal: tackling the metabolic dysfunction at the core of liver disease.
In October, we also presented updated findings from vanoglipel at the H.C. Wainwright Liver Disease Virtual Conference, adding further evidence that the compound may play a leading role in the next generation of MASH treatments.
Investment and industry dynamics
According to Evaluate Pharma, the global market for MASH treatments could exceed $20 billion by 2030, with major players from Novo Nordisk to Madrigal and Viking Therapeutics shaping the competitive landscape.
Still, recent data from Forrester and other industry analysts caution that AI-driven drug discovery investment is facing a short-term correction, as investors shift focus from pure technology bets to programs showing translational and clinical traction. In this environment, companies with validated clinical data, particularly in high-need areas like MASH, stand out. One of the most compelling lessons from recent MASH research is that the liver is both a victim and a driver of metabolic dysfunction. Improvements in hepatic fat content and fibrosis often correlate with gains in glycemic control, lipid balance, and cardiovascular health.
This has profound implications for how therapies are developed and evaluated. Future clinical endpoints will likely extend beyond histological improvement to include systemic outcomes such as HbA1c reduction, body weight, and cardiovascular risk markers.
MetaVia is designing its next-stage studies to reflect this broader perspective aligning with regulatory agencies’ growing recognition that metabolic restoration is as important as fibrosis regression.
As we move into 2026, the MASH field is poised for transformation. The convergence of advanced biomarkers, AI-enabled trial design, and multimodal therapies will accelerate discovery and improve patient stratification.
The next frontier in MASH will not be defined by a single molecule but by a new ecosystem of data, insight, and collaboration that aligns innovation with patient need.
The Novo Nordisk-Akero deal is a signal that the industry has reached an inflection point. MASH is no longer an orphaned field; it is central to the future of cardiometabolic care. As more therapies reach late-stage development, the challenge ahead will be translating this scientific and investment momentum into real clinical impact. That means not only developing effective drugs but also ensuring early diagnosis, better patient stratification, and accessible care pathways to pioneer therapies that redefine what’s possible in metabolic health. MASH is just the beginning.
Newsletters
Receive the latest pharmaceutical news, personalities, education, and career development – weekly to your inbox.
