Orforglipron Advances in Phase III as Oral Non-Peptide GLP-1R Agonist for Obesity and Diabetes
Orforglipron, an oral non-peptide GLP-1R partial agonist developed by Chugai and Eli Lilly, has reported positive Phase III data for obesity and type 2 diabetes, representing a shift from injectable peptides to oral small molecules in the GLP-1R space.
Orforglipron, an oral non-peptide GLP-1R partial agonist in Phase III for obesity and type 2 diabetes mellitus, has recently read out positive data. The molecule was first discovered by Chugai Pharmaceuticals under the name OWL833, then licensed by Eli Lilly for worldwide development under the name LY3502970.
The compound was nominated as a Molecule of the Year in both 2020 and 2023, initially when it was still in Phase I. Orforglipron was discovered from an LLC-PK1 cell high-throughput screen followed by optimization.
GLP-1R agonists have reshaped the treatment landscape for diabetes and obesity and are now being explored across a range of new indications. The therapeutic and commercial value of GLP-1R has risen to become a $150B+ target. Notable clinical programs range from injectable peptides like semaglutide to oral small molecules like orforglipron, with varying mechanisms, efficacy, and stages of development.
Orforglipron represents a pioneering approach as an oral non-peptide alternative to the injectable peptide GLP-1R agonists that have dominated the market. The molecule's development includes cryo-EM structural studies that have informed its design and optimization.