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In short, robust studies in rodents demonstrate that all GLP-1RAs may cross the BBB but at largely variable rates and speed, seemingly higher for older agents (eg, exenatide, lixisenatide) and lower for newer ones (eg, semaglutide, tirzepatide).100 101 Even the larger and/or more electrically charged compounds, such as semaglutide, could still reach the brain via circumventricular sites and active transporters.102 103 Other mechanisms, such as brain capillary binding or sequestration, have been understudied.99 Interactions between the endogenous GLP-1 system, both peripheral and central, and how these may be perturbed by exogenous GLP-1RAs are unclear.104 105 Translating these findings in humans is complex

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This allows Tirzepatide patients to feel fuller faster and for more extended periods of time