HISHS-2001

HISHS-2001 is a novel dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the gastric inhibitory polypeptide receptor (GIPR). It is characterized by a biased signaling profile at the GLP-1R, favoring cAMP generation over β-arrestin 2 recruitment, which is associated with reduced receptor internalization and recycling compared to the dual agonist tirzepatide. Preclinical studies in obese hyperglycemic *db/db* mice have demonstrated that HISHS-2001 effectively increases circulating insulin, lowers HbA1c, and reduces body weight at substantially lower doses than tirzepatide. This improved pharmacological profile suggests potential for enhanced efficacy and a better tolerability profile in the treatment of metabolic disorders such as type 2 diabetes and obesity.