Tirzepatide knee replacement trial keeps enrolling, with main results due in 2027

STOP KNEE-OA, a phase 4 trial of tirzepatide in adults with obesity and knee osteoarthritis, is continuing to enroll participants, according to its registration on ClinicalTrials.gov ^[1]. The study is built around an unusual question: whether the drug changes how many people who are already candidates for a knee replacement actually go on to have the surgery ^[1]. No results have been reported yet.

What the trial is testing

The study, listed as NCT06191848, is sponsored by the University of Melbourne, with Eli Lilly as a collaborator ^[1]. It plans to randomize 352 adults who have obesity and moderate-to-severe knee osteoarthritis and who are already eligible for a knee replacement waiting list ^[1].

Participants are assigned to 72 weeks — about a year and a half — of either tirzepatide or placebo ^[1]. Tirzepatide is the molecule in the injected drugs Mounjaro and Zepbound, which are approved for other uses.

The primary endpoint is the percentage of participants in each group who go on to have knee replacement surgery ^[1]. That means the operation itself, not a pain score or an imaging measurement, is the main thing the trial is designed to answer. The trial record does not describe how the researchers expect the drug to affect that decision, and it does not say whether participants receive other treatments such as physical therapy or weight counseling.

Because the study is randomized and compares against placebo, some participants will receive placebo injections for the full 72 weeks rather than tirzepatide ^[1].

Why it matters for patients

Knee replacement is a major operation, and the people this trial is enrolling are already far enough along that their doctors have put them on a waiting list for one ^[1]. If a medication could delay or prevent that surgery for some of them, it would change a decision that many patients with obesity and knee osteoarthritis currently face. Whether tirzepatide does that is unknown; this trial is one of the first attempts to measure it directly, and no outcome data exist yet ^[1].

For patients, two practical points stand out. First, the trial only enrolled people who already meet the criteria for a knee replacement waiting list, so any future findings would apply most directly to that group, not to everyone with knee pain ^[1]. Second, the endpoint is surgery, not symptom relief, so a result showing less pain would not by itself be the main finding of this study.

Tirzepatide is not approved to treat knee osteoarthritis, and this trial would not by itself change that. The record does not say what the researchers or the sponsor plan to do with the results, or whether they intend to seek a new approved use.

What happens next

The registry lists an estimated primary completion date of May 2027, which is when the main measurements are expected to be finished rather than when results would be published ^[1]. The trial is still enrolling, and a date for finishing enrollment has not been disclosed ^[1]. A timeline for releasing results after May 2027 has not been reported ^[1].

People who want to know whether they might qualify, where the study is running, or what participation involves would need to check the trial record or contact the study team directly ^[1].