Lilly Launches Phase 3 Trial of Oral Small-Molecule GLP-1 Agonist Orforglipron for Knee Osteoarthritis Pain in Patients with Obesity

▎Armstrong

On September 4, 2025, Eli Lilly registered a Phase III clinical trial, ATTAIN-OA PAIN, on Clinicaltrials.gov for the small molecule GLP-1 receptor agonist Orforglipron in treating knee osteoarthritis combined with obesity.

This Phase III clinical trial plans to enroll 800 patients with knee osteoarthritis and obesity, and is expected to be completed in 2028.

The primary endpoint of this Phase III clinical trial was the WOMAC pain score.

Orforglipron has already succeeded in Phase III clinical trials for diabetes and obesity, and an application for market approval will soon be submitted. It is set to become the world’s first small-molecule GLP-1 receptor agonist.

Eli Lilly is actively exploring new indications for Orforglipron, and has successively initiated phase III clinical trials for hypertension and osteoarthritis pain.

In October 2024, Novo Nordisk published the phase three clinical trial results of semaglutide for the treatment of osteoarthritis pain in the New England Journal of Medicine, indicating that semaglutide...Meglutide can significantly reduce body weight and significantly alleviate pain caused by obesity-related knee osteoarthritis. Its analgesic effect is comparable to that of opioids and can improve the ability to participate in physical activities.

Summary

The indications explored for Orforglipron include diabetes, obesity, obstructive sleep apnea (OSA), hypertension, and osteoarthritis pain, among others.