NASH
The 4-letter acronym for a liver issue treated with GLP-1 agonists is NASH (Nonalcoholic Steatohepatitis). 1
What is NASH?
NASH is the inflammatory form of nonalcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, hepatocellular ballooning, and lobular inflammation, which can progress to fibrosis and cirrhosis. 1
GLP-1 Agonist Treatment Evidence
GLP-1 receptor agonists are promising agents for NASH treatment, though their role is not yet fully defined and requires further investigation. 1
Specific GLP-1 Agonists with Evidence:
- Semaglutide (0.4 mg/day) achieved NASH resolution without worsening fibrosis in 59% of patients versus 17% in placebo group (p<0.001) 2
- Liraglutide demonstrated more frequent resolution of NASH (9/23 versus 2/22; p=0.019) and less progression of fibrosis (2/23 versus 8/22; p=0.04) compared to placebo in the LEAN trial 2
- Tirzepatide (dual GIP/GLP-1 agonist) showed robust evidence for histological improvements in steatosis, hepatocellular ballooning, and lobular inflammation 3
Current Limitations:
Until further data are available, the use of GLP-1 receptor agonists is premature for the treatment of lean NASH but may be considered in the management of comorbid metabolic conditions such as type 2 diabetes mellitus (T2DM). 1
- GLP-1RAs improve steatosis and inflammation but have not consistently demonstrated significant improvement in fibrosis 4, 3
- Most clinical trials have been enriched with overweight and obese patients, limiting generalizability to lean NASH patients 1
- No GLP-1RAs are currently FDA-approved specifically for NASH treatment 2
Related Terminology:
The newer umbrella term MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) has replaced NAFLD, with MASH (Metabolic dysfunction-Associated Steatohepatitis) replacing NASH in the most recent nomenclature. 1, 5