In this substudy of participants with MASLD who were included in a phase 2 study of people with obesity or overweight with weight-related complications, treatment for 24 weeks with the GIP/GLP-1/GCG triple receptor agonist, retatrutide, was associated with significant reductions in liver fat content at all doses. This evidence concerns the gene GCG and obesity due to melanocortin 4 receptor deficiency.