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Tirzepatide may cause gastrointestinal adverse effects that could lead to dehydration, potentially compounding hypotension risk, particularly in patients taking diuretics or renin-angiotensin system blockers

The substitution (Y10 P in tirzepatide) and modification (lipidated K10 P in peptide 20) stabilized the binding of dual and triple agonists by newly-formed interactions with residues surrounding the TM1-TM2 cleft, a phenomenon unseen in the case of GLP-1 27