The dual GLP-1/glucagon receptor agonist JNJ-64565111 (efinopegdutide) was compared with placebo and liraglutide 3.0 mg in a 26-wk multicenter study in 474 subjects with high-grade obesity (BMI 35–50 kg/m2) without diabetes. This evidence concerns the gene GCG and obesity due to melanocortin 4 receptor deficiency.