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Substitution of these critical leucine residues to tryptophan eliminated binding affinity, highlighting the importance of maintaining key hydrophobic contacts of leucine side chains, and not general hydrophobicity, which is further exemplified by the evolutionary conservation of leucine residues in LD motifs 41

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Most common side effects were gastrointestinal, with 24.5% of participants in the phase 2 obesity trial discontinuing efinopegdutide 10 mg due to AE however when the same dose was used with gradual escalation at the MASLD trial (starting dose 2.4 mg for 4 weeks, then 5 mg for 4 weeks and then 10 mg), only 5.6% of participants discontinued the medication due to AE