This lack of association may be due to either insufficient metabolic improvement by GLP-1 RAs over the intervention period of 12 weeks to affect FGF21 levels, insufficient changes in key regulatory factors such as hepatic fat, inflammation, and nutritional status, or the presence of FGF21 resistance in obesity and metabolic disease limiting responsiveness to GLP-1 RA. This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.