Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 38858523 · doi:10.1038/s41591-024-03018-2
What was done
This was a randomized, double-blind, placebo-controlled phase 2a substudy embedded within a 48-week phase 2 obesity trial. Ninety-eight participants with metabolic dysfunction-associated steatotic liver disease (MASLD) and baseline liver fat of 10% or greater were randomized to once-weekly subcutaneous retatrutide (1 mg, 4 mg, 8 mg, or 12 mg) or placebo. The primary endpoint was the mean relative change from baseline in liver fat percentage at 24 weeks.
What was found
At 24 weeks, the mean relative change in liver fat from baseline was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg), and +0.3% with placebo (all P < 0.001 vs placebo). Normal liver fat (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg), and 0% (placebo) of participants. Liver fat reductions correlated significantly with reductions in body weight, abdominal fat, and markers of insulin sensitivity and lipid metabolism.
Why it matters
Triple agonism with retatrutide achieved marked, dose-dependent reductions in hepatic steatosis, normalizing liver fat in most patients receiving higher doses.
Limits
The sample size was small (n = 98 across five arms). The study evaluated non-invasive liver fat percentage at 24 weeks rather than histological outcomes like fibrosis or NASH resolution via biopsy, and safety/tolerability outcomes were not reported in the abstract.
Cited by
- supports Retatrutide's glucagon receptor activation combined with GLP-1 and GIP agonism leads to significant weight reduction and marked improvements in liver fat and NASH.