A Nature Medicine analysis of SELECT trial data found that semaglutide reduced major adverse cardiovascular events (MACE) in participants at high risk of liver fibrosis and improved the fatty liver index over 104 weeks, adding to the growing evidence for GLP-1 hepatic benefits. Historical articles may no longer reflect current regulatory status. Check the cited primary source.
A secondary analysis of the SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) published in Nature Medicine examined outcomes specifically in participants at high risk of liver fibrosis.
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The SELECT trial enrolled 17,604 overweight or obese adults with established cardiovascular disease but without diabetes — one of the largest cardiovascular outcomes trials ever conducted.
In the liver fibrosis high-risk subgroup, semaglutide demonstrated:
Non-alcoholic fatty liver disease (NAFLD) and its inflammatory progression to non-alcoholic steatohepatitis (NASH) and fibrosis represent one of the most significant unmet medical needs in metabolic medicine. Patients with advanced liver fibrosis have substantially elevated cardiovascular risk independent of other risk factors.
GLP-1 receptor agonists have been hypothesized to have direct hepatic effects — reducing hepatic fat accumulation, liver inflammation, and potentially fibrogenesis — in addition to their systemic metabolic effects. This analysis provides outcome-level data supporting the cardioprotective benefit in the subgroup most likely to benefit from GLP-1 hepatic effects.
This analysis adds to what is becoming a very broad evidence base for GLP-1 receptor agonists extending beyond their original metabolic indications:
PeptideX tracks GLP-1 compound profiles including semaglutide, tirzepatide, retatrutide, liraglutide, and cagrilintide across all six categories in the index.
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A secondary analysis of the SELECT trial published in Nature Medicine found that semaglutide reduced major adverse cardiovascular events in participants at high risk of liver fibrosis and significantly improved the fatty liver index over 104 weeks, supporting potential hepatic benefits from GLP-1 receptor agonism.
Semaglutide is not FDA-approved for NASH or liver fibrosis as of Q1 2026. However, multiple clinical trials are ongoing, and the SELECT subgroup analysis adds outcome-level data supporting the biological plausibility of hepatic benefit. Dedicated NASH trials with histological endpoints are required for regulatory approval.
SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) is a randomized controlled trial that enrolled 17,604 overweight or obese adults with cardiovascular disease but without diabetes. The primary results showed a 20% relative risk reduction in major adverse cardiovascular events with injectable semaglutide versus placebo.