What you need to know.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as NAFLD, is now the most common chronic liver condition worldwide. It is strongly associated with obesity and type 2 diabetes, and while many patients remain asymptomatic, progression to metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis substantially increases the risk of cirrhosis, hepatocellular carcinoma, and cardiovascular disease.

For GPs, identifying at-risk patients and considering effective therapies early is crucial, as intervention can alter the natural history of disease and reduce long-term morbidity and mortality.

Evidence Summary

Recent data shows that GLP-1 receptor agonists, particularly semaglutide, are a safe and effective therapy for MASLD. The ESSENCE phase 3 trial (2025) demonstrated that semaglutide 2.4 mg weekly (Wegovy®) achieved MASH resolution in 63% of participants compared with 34% on placebo, and fibrosis improvement (≥1 stage) in 37% compared with 22% on placebo at 72 weeks.

Earlier phase 2 studies had already highlighted the benefit in resolving steatohepatitis, but the new evidence confirms that higher-dose therapy can also improve fibrosis. Importantly, benefits appear less pronounced in cirrhosis, where histological reversal was not achieved, although weight loss and liver fat reduction were still observed.

Who Benefits most?

Patients most likely to benefit are those with obesity and/or type 2 diabetes, in whom weight reduction and metabolic improvements are already indicated. Since weight loss of ≥5–10% improves steatohepatitis and ≥10% can lead to fibrosis regression, GLP-1 receptor agonists provide a valuable tool to help patients achieve these targets.

A simple FIB-4 score can help guide decision-making in primary care:

  • <1.3 → low risk (continue management in primary care)
  • 1.3–2.7 → indeterminate (arrange elastography)
  • 2.7 → high risk (refer to hepatology)
Practical Use in Australia (September 2025)

At present, semaglutide is not TGA-approved for MASLD/MASH and prescribing in this setting is off-label. However, it is available on-label for other indications:

  • Wegovy® 2.4 mg weekly is approved for chronic weight management and cardiovascular
  • event reduction in patients with obesity and established CVD.
  • Ozempic® remains approved for the management of type 2 diabetes.

For patients with MASLD/MASH and obesity or T2D, use may be considered off-label in consultation with a specialist, with careful documentation of rationale and shared decision-making.

Safety Considerations

As with other GLP-1 receptor agonists, the main adverse effects are gastrointestinal (nausea, vomiting, constipation), which are generally transient and dose-dependent. Rare but important risks include pancreatitis and malnutrition in some patients with liver cirrhosis.

Caution is advised in patients with a history of diabetic retinopathy (due to rapid improvements in HbA1c) and it should be avoided in individuals with a personal or family history of medullary thyroid carcinoma or MEN2. Current peri-procedural guidance also recommends considering temporary cessation before procedures requiring anaesthesia if aspiration risk is a concern.

Take home message

GLP-1 receptor agonist therapy with semaglutide (at the 2.4 mg weekly Wegovy® dose) is the first treatment to demonstrate both resolution of MASH and improvement in fibrosis in phase 3 trials. While not yet approved by the TGA for MASLD/MASH, it is a reasonable option to consider off-label in patients with liver fibrosis from MASLD (in consultation with a specialist), obesity or type 2 diabetes who have high-risk disease, alongside lifestyle modification and cardiovascular risk management.

For GPs, early risk stratification with FIB-4 and timely referral remain key, while pharmacotherapy may soon shift the treatment paradigm for this increasingly common condition.