There is a reason the pharmacology of the new weight loss pills has been harder to study than the injections, and it is not funding or interest. It is that the drugs barely work in laboratory animals.
Small-molecule GLP-1 receptor agonists, the class that includes the FDA-approved oral drug orforglipron, bind selectively to the human receptor and not well to the rodent one. That single fact stalled mechanistic research on an entire drug class. A team at the University of Virginia solved it by building mice whose GLP-1 receptors had been gene-edited to behave like human ones, and the circuit they found once the drugs finally worked was not the one anyone expected.
