In the SURPASS-2 trial, patients with obesity and T2D who received tirzeapatide (5 mg weekly) achieved greater HbA1c and body weight reductions than those receiving semaglutide (1 mg weekly) during the 40 week study (64) despite comparable putative GLP-1R occupancy at these doses (47). This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.