The co-administration of GLP-1 and PYY3-36 in humans also reduced energy intake compared with placebo and more than the sum of the individual infusions, demonstrating a synergistic effect.138,139 A long-acting PYY analogue in combination with semaglutide is now being assessed in a phase 2 study as treatment for obesity (NCT04969939). Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.