Rational Design of Dual-Target Molecules via a Fragment-Merging Strategy: TGR5 Agonism and SSTR5 Antagonism

improved glucose tolerance and alleviated gallbladder filling at pharmacologically relevant doses. Collectively, these findings establish a proof of concept for dual TGR5/SSTR5 modulation as a promising therapeutic modality, providing a viable strategy to achieve potent metabolic efficacy with reduced risk of adverse effects.