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The development of dual GIPRGLP1R coagonists that bind to either one or the other receptor (sequence-mixed dual agonists) has emerged as an innovative therapeutic strategy for obesity and type 2 diabetes

While the overall frequency of liver enzyme elevations across the over 1,400 participant safety database of danuglipron is in-line with approved agents in the class, a single asymptomatic participant in one of the dose-optimization studies experienced potential drug-induced liver injury which resolved after discontinuation of danuglipron

Our results reveal the existence of residue networks crucial for unimolecular agonist-mediated receptor activation and their distinct signaling patterns, which might be useful to the rational design of biased drug leads.

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