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Preclinical studies with other GLP-1 receptor agonists have demonstrated limited brain uptake, suggesting minimal blood-brain barrier penetration, though tirzepatide-specific human data are limited

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Brzoska T, Luger TA, Maaser C, Abels C, Bhm M

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The pen design intentionally limits dose selection to FDA-approved increments, providing an additional safety mechanism against accidental overdosing

This means the problem is not caused by just one factor, but by several changes happening at the same time