Receptor occupancy analysis demonstrates that 5 mg weekly tirzepatide engages the GLP-1R to a similar degree as 1 mg weekly semaglutide (47); at this dose, tirzeaptide drives ~8.3% weight loss compared to 6.6% for semaglutide over 40 weeks in the head-to-head SURPASS-2 trial in patients with obesity and T2D. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.