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The Aib residue at position 2 and the fatty acid modification both confer resistance to the primary degradation enzymes (DPP-4 and neprilysin), extending the metabolic half-life

This 90-day lag was implemented to account for the time required for GLP-1 RAs to exert potential neuromodulatory effects and to minimize reverse causality

These reactions can appear anywhere on the body but are most commonly observed on the arms, legs, and torso

PMID: 21989665

If headaches on tirzepatide persist despite drinking 2-3 liters of water daily, switch to electrolyte-enhanced water for a few days and see if the pattern changes