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In contrast, the bulkier Y37 rAmy in rAmy-bound AMY 2 R prevents equivalent interactions of N35 rAmy with RAMP2, and instead the bulkier Y37 rAmy forms interactions with E101 RAMP2 and F111 RAMP2 stabilising the peptide at the CTR/RAMP ECD interface in the bypass conformation

Analyses included the effects of various dosing conditions (such as fasting time and water volume), demographic covariates and variability in exposure following single and multiple oral administration

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Cardiovascular data on endpoints like MACE-3 or MACE-4 are presently not available yet, but an early meta-analysis demonstrated at least cardiovascular safety in patients with T2D treated with tirzepatide (78, 79)