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However, systemic administration is hindered by poor blood-brain barrier (BBB) permeability, dose-limiting toxicity, and poor patient compliance due to frequent dosing regimens

SURMOUNT-1: Tirzepatide 15 mg, the generational leap of 2022 SURMOUNT-1 (Jastreboff et al., NEJM 2022, PMID 35658024) randomized 2,539 obese adults without diabetes to tirzepatide 5, 10, or 15 mg/week or placebo over 72 weeks