STOP KNEE-OA, the first trial of tirzepatide for knee replacement, continues enrolling

A clinical trial called STOP KNEE-OA has begun enrolling adults with obesity and moderate-to-severe knee osteoarthritis who already qualify for a knee replacement waiting list, to see whether tirzepatide can change the course of their disease ^[1]. The University of Melbourne is running the study with Eli Lilly, the maker of tirzepatide, listed as a collaborator ^[1]. Tirzepatide is sold in the United States as Mounjaro for type 2 diabetes and Zepbound for weight management ^[1].

The trial plans to randomize 352 participants to either 72 weeks of once-weekly tirzepatide injections or a placebo ^[1]. All participants have obesity along with knee osteoarthritis severe enough that they are already eligible to be placed on a waiting list for knee replacement surgery, a detail that sets this study apart from most other GLP-1 trials, which typically look at weight loss or blood sugar as the main outcome ^[1].

The primary endpoint of the trial is not weight loss or pain scores by themselves. Instead, researchers will track what percentage of participants in each group go on to actually have a knee replacement operation during the study period ^[1]. This design directly tests whether the drug can reduce or delay the need for surgery, rather than just easing symptoms. The trial is registered as a phase 4 study, meaning it is testing an already-approved drug in a new context rather than seeking initial approval ^[1]. Primary completion is estimated for May 2027 ^[1].

Why it matters for patients

Knee osteoarthritis is a common reason adults, especially those with obesity, end up needing joint replacement surgery. Excess weight puts added strain on the knee joint, and losing weight is already known to ease some arthritis symptoms. What has not been established is whether a GLP-1 drug like tirzepatide can meaningfully reduce the number of people who eventually need surgery, or how long it might delay that surgery for those who are already considered candidates for it ^[1].

Because this trial is placebo-controlled and enrolls people already on a surgical waiting list, its results could speak directly to a question many patients and their doctors face: whether to pursue weight-loss medication as a way to potentially avoid or postpone an operation, or move ahead with surgery on the usual timeline. However, no results are available yet, and the study will not reach its primary completion milestone until 2027 ^[1]. Patients considering tirzepatide for any reason should know that its effect on the actual need for knee replacement surgery remains unproven and is precisely what this trial is designed to test ^[1].

It is also not yet known from the available trial information how researchers will handle participants who choose to have surgery during the 72-week treatment period, what pain or function scores will be tracked as secondary measures, or what side effects investigators expect to see over such an extended dosing period in this specific population. Those details are not addressed in the source material reviewed here.

What happens next

The trial continues to enroll participants as of the most recent update, with a target of 352 people ^[1]. Primary completion, when the main knee replacement outcome data should be available, is estimated for May 2027 ^[1]. Until that point, there is no efficacy or safety data from this study for patients or doctors to review, and the trial's design and enrollment status are subject to change as reported on ClinicalTrials.gov ^[1].