Home › Trials › NCT07153471

Orforglipron for adults with overweight or obesity and knee osteoarthritis

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

PHASE3 · Eli Lilly and Company · NCT07153471

This will test whether orforglipron helps adults with overweight or obesity and knee osteoarthritis lose weight and ease knee pain over about 74 weeks.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment800 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company (industry)
Locations95 sites (Phoenix, Arizona and 94 other locations)
Trial IDNCT07153471 on ClinicalTrials.gov

What this trial studies

Two parallel Phase 3 studies under the GZPT master protocol will randomize adults with BMI ≥27 and symptomatic knee osteoarthritis to receive oral orforglipron or matching placebo and follow them for about 74 weeks. Participants must have tried to lose weight previously and meet clinical criteria for knee OA, while key exclusions include diabetes, recent GLP‑1 use, major recent weight change, bariatric surgery, active knee infection, or recent serious heart conditions. Study endpoints will include changes in body weight, knee pain and function, and safety monitoring throughout treatment. The trials are sponsored by Eli Lilly and conducted at clinical sites in Arizona and California.

Who should consider this trial

Good fit: Adults with a BMI of 27 or higher who have symptomatic knee osteoarthritis, have tried and not succeeded at weight loss, and meet the study's medical eligibility (for example no diabetes and no recent GLP‑1 use) are the intended participants.

Not a fit: People with any form of diabetes, recent major weight change, planned or recent bariatric surgery, active knee infection, recent severe heart problems, or who used a GLP‑1 agonist within 180 days would be excluded and are unlikely to participate or benefit from this study.

Why it matters

Potential benefit: If effective, orforglipron could produce clinically meaningful weight loss that may reduce knee pain and improve function for people with knee osteoarthritis.

How similar studies have performed: Other GLP‑1 receptor agonists and weight‑loss medications have produced substantial weight loss and some evidence links weight loss to reduced knee pain, but orforglipron itself is a newer oral agent now being tested in Phase 3.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Have a body mass index (BMI) of 27 kilograms per square meter (kg/m2) or higher at screening
* Have tried at least once to lose weight through diet but were unsuccessful
* Have osteoarthritis of the knee and at least one of the following conditions:

  * Be over 50 years old
  * Have morning knee stiffness that lasts about 30 minutes
  * Have a crackling or grinding sound or feeling in the knee

Exclusion Criteria:

* Have gained or lost more than 11 pounds within 90 days prior to screening
* Have had a surgery for obesity or plan to have one in the next 18 months
* Have an active knee infection
* Have type 1 diabetes, type 2 diabetes, or any other type of diabetes
* Have had a recent heart condition or New York Heart Association Functional Classification Class IV congestive heart failure
* Have used any glucagon-like peptide-1 (GLP-1) receptor agonist medication within 180 days of screening

Where this trial is running

Phoenix, Arizona and 94 other locations

+45 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Osteoarthritis, Arthritis, Overnutrition, Nutrition Disorder, Joint Diseases, Musculoskeletal Disease, Knee Degeneration, Osteoarthrosis

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.