A Phase 3 Study to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee: A Multicenter, Randomized, Double-Blind, Parallel-Arm, Placebo-Controlled Trial

Clinical Trial20 Mar 2026Phase 3● 6/10i

A Phase 3 Study to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee: A Multicenter, Randomized, Double-Blind, Parallel-Arm, Placebo-Controlled Trial

Eli Lilly and Company

Phase 3 trial evaluating orforglipron once daily in people with obesity or overweight and osteoarthritis of the knee. The study targets 800 participants over 74 weeks in a placebo-controlled design, measuring pain reduction via the WOMAC Pain Subscale. This represents Eli Lilly's push to expand orforglipron beyond type 2 diabetes into new indications where GLP-1s show promise. The trial combines weight loss with joint pain relief, targeting a large patient population not directly addressed by current obesity medications.

Strategic Signal

Eli Lilly is leveraging orforglipron's weight loss profile to enter the musculoskeletal pain market, creating a differentiated positioning versus Novo's semaglutide obesity franchise. The WOMAC pain endpoint could support dual claims for weight reduction and symptom management in arthritis. US payers may favor combination benefits over weight-only indications, given the high prevalence of osteoarthritis in people with obesity and potential cost offsets from reduced orthopedic interventions.

GLP-1Weight lossEli Lilly

Original Abstract

The GZPT master protocol will support two independent studies, J2A-MC-GZT1 and J2A-MC-GZT2. Each study will see how well and safely orforglipron works in people with obesity or overweight who have osteoarthritis (OA) of the knee with pain. Participation in the study will last about 74 weeks. | Condition(s): Osteoarthritis | Primary endpoint(s): Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | Enrollment: 800 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2028-04 | Status: Recruiting | Last update: 2026-03-20

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