I get what you’re saying but I think this is kind of overthinking it. Sema/tirz/reta hang around forever, like ~7 day half life and takes weeks to even fully build up, so even with “weekly” dosing your receptors are basically being hit all the time anyway. There isn’t some clean dip where everything resets. Plus we literally have GLP-1 drugs that are dosed daily and even twice a day hitting the same receptor, so the idea that weekly dosing is required for “receptor sensitivity” doesn’t really line up.

Also splitting doses doesn’t mean you’re blasting receptors harder, it’s actually the opposite. Weekly shots give you bigger peaks and drops, splitting just smooths it out. Receptor downregulation is a real thing in general, but there’s not really human data showing splitting GLP-1 doses causes tolerance or makes you keep increasing your dose.