Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders

Abstract

This PhD project investigates the preclinical safety, efficacy, and pharmacokinetics (PK) features of novel GPR119 agonists, ps297 and ps318, for metabolic disorders. Both investigational compounds act as GLP-1 secretagogues, showing synergistic effects with sitagliptin. PK analysis confirmed a gut-oriented mechanism with low bioavailability. Its chronic combination therapy with sitagliptin restored incretin and insulin secretion, glucose homeostasis, and liver health in obese mice. Toxicity assessments indicated safety, supporting further investigation of these gut-oriented agents to treat metabolic disorders.