An alternative explanation is that with a once-weekly GLP-1 receptor agonist, differences in drug exposure might occur throughout the inter-injection interval that affect the efficacy and tolerability profile. The latter explanation would also apply to the head-to-head comparison between once-weekly exenatide and liraglutide.12 Finally, albiglutide is a large protein that cannot cross the blood–brain barrier or diffuse into the hypothalamus and area postrema (vomiting centre) as easily as do smaller peptides such as liraglutide. Both efficacy measures and adverse events have been partly linked to centrally mediated effects.22,23