Semaglutide and retatrutide reduced knee pain in people with obesity and knee osteoarthritis. In STEP 9, pain on the WOMAC scale fell by 41.7 points out of 100 on semaglutide and by 27.5 points on placebo. In TRIUMPH-4, retatrutide 12 mg lowered pain by an average of 4.5 points out of 10 and body weight by 28.7 percent. Below we describe both trials and where the pain relief comes from.
Why does body weight matter for the knees?
The knee carries body weight with every step, so each extra kilogram increases its load. The authors of STEP 9 point out that earlier studies had already shown relief of knee pain after weight loss. What was new was the question of whether GLP-1 medicines would give such an effect with a large drop in weight.
In both trials pain was measured with the WOMAC scale. This is a questionnaire on joint pain, stiffness and function, in which a higher score means more complaints. STEP 9 used a scale from 0 to 100, and the retatrutide trials a scale from 0 to 10.
What did STEP 9 show?
STEP 9 included 407 people with obesity and moderate knee osteoarthritis, with at least moderate pain. Average BMI was 40.3, and the average pain score 70.9 points out of 100. Participants received semaglutide 2.4 mg or placebo for 68 weeks, both groups together with diet and exercise advice. The results were published in 2024 in the New England Journal of Medicine.
| STEP 9, after 68 weeks | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Weight loss | 13.7 percent | 3.2 percent |
| Fall in pain on the WOMAC scale (0 to 100) | 41.7 points | 27.5 points |
| Improvement in physical function (SF-36) | 12.0 points | 6.5 points |
| Stopped because of side effects | 6.7 percent | 3.0 percent |
Pain fell from about 71 to about 29 points, so by more than half. Physical function improved almost twice as much as on placebo. Serious side effects occurred about equally often in both groups.
What did TRIUMPH-4 show?
TRIUMPH-4 is a retatrutide trial designed only for people with knee osteoarthritis. It included 445 adults with a BMI of at least 27 and lasted 68 weeks. Lilly announced its results on 11 December 2025. As of 6 October 2026 we had not found a full publication of this trial in PubMed.
| TRIUMPH-4, after 68 weeks | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
|---|---|---|---|
| Weight loss | 26.4 percent | 28.7 percent | 2.1 percent |
| Fall in pain on the WOMAC scale (0 to 10) | not reported | 4.5 points | 2.4 points |
| Stopped because of side effects | 12.2 percent | 18.2 percent | 4.0 percent |
At the 12 mg dose, 58.6 percent of participants lost at least 25 percent of their weight, and 39.4 percent lost at least 30 percent. At least 35 percent of body weight was lost by 23.7 percent of people on this dose.
What did the knee pain group in TRIUMPH-1 show?
TRIUMPH-1 also included 574 people with knee osteoarthritis, assessed separately. Its results were published on 29 September 2026 in the New England Journal of Medicine. After 80 weeks pain fell more in all retatrutide groups than on placebo.
| TRIUMPH-1, knee pain group | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Fall in pain on the WOMAC scale | 3.4 points | 3.9 points | 4.1 points | 2.5 points |
The figures in the table cover all participants in this group, including those who stopped treatment. The difference from placebo at the 9 and 12 mg doses was 1.4 and 1.6 points.
What other benefits did these trials show?
In the same trials more than knee pain improved. In STEP 9, physical function in the SF-36 questionnaire rose by 12.0 points on semaglutide and by 6.5 points on placebo. This is a scale from 0 to 100, in which a higher score means better physical wellbeing.
In TRIUMPH-1, retatrutide also reduced the number of breathing pauses during sleep in 243 people with sleep apnoea. The number of pauses and shallow breaths fell by 22.8 per hour at 4 mg, by 34.3 at 9 mg and by 32.1 at 12 mg. On placebo the fall was 9.6 per hour.
Where does the pain relief come from?
The simplest explanation is less load on the joint with lower body weight. However, STEP 9 and TRIUMPH did not separate the effect of weight alone from any other action of the medicine.
The placebo groups, who received the same diet and exercise advice, also felt clear relief, by 27.5 points in STEP 9. The medicines therefore gave additional relief beyond what lifestyle changes alone give. The relief went hand in hand with better function in daily life.
What to watch out for?
With retatrutide 12 mg in TRIUMPH-4, 18.2 percent of people stopped treatment because of side effects. That is more than in the trials on obesity alone. The most commonly reported effects were nausea, diarrhoea, constipation, vomiting, reduced appetite and unusual skin sensations.
With semaglutide in STEP 9, 6.7 percent stopped, mainly because of stomach complaints. Neither medicine treats osteoarthritis itself, and the data concern people with obesity. Treatment of joint disease is managed by a doctor.
Where to buy semaglutide and retatrutide?
The shop offers semaglutide 3 mg Bio-Peptide for 90 EUR, in stock. Retatrutide is available as 20 mg Bio-Peptide for 200 EUR in stock, 20 mg Genheal for 200 EUR on backorder and 40 mg Nouveaux in a pen for 350 EUR in stock.
The products in the shop are material for laboratory research, not medicines. Retatrutide is not approved in any country. The results of retatrutide over the months are described in the guide on retatrutide results, and the result of each dose in the guide on retatrutide doses in trials.
Frequently asked questions
Does semaglutide reduce knee pain?
In STEP 9, knee pain on the WOMAC scale fell after 68 weeks by 41.7 points out of 100 with semaglutide and by 27.5 points with placebo.
Does retatrutide help with knee pain?
In TRIUMPH-4, retatrutide 12 mg lowered pain by 4.5 points out of 10, and placebo by 2.4 points. Body weight fell by 28.7 percent.
Why do obesity medicines reduce knee pain?
Most likely through less load on the joint after weight loss. The trials did not separate the effect of weight alone from any other action of the medicine.
Does knee pain also fall without the medicine?
Yes, in STEP 9 pain fell by 27.5 points on placebo with diet and exercise. Semaglutide gave an extra 14.2 points on top of that result.
How many people stopped treatment?
In STEP 9, 6.7 percent of people on semaglutide stopped, and in TRIUMPH-4, 18.2 percent on retatrutide 12 mg and 12.2 percent on 9 mg.
Sources
- Bliddal H, Bays H, Czernichow S et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. New England Journal of Medicine, 2024, 391(17): 1573-1583. https://doi.org/10.1056/NEJMoa2403664
- Jastreboff AM, Kaplan LM, Davies MJ et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. New England Journal of Medicine, 2026. https://doi.org/10.1056/NEJMoa2604169
- Giblin K, Kaplan LM, Somers VK et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. Diabetes, Obesity and Metabolism, 2026, 28(1): 83-93. https://doi.org/10.1111/dom.70209
- The Pharmaceutical Journal. Investigational weight-loss drug trial shows average reduced body weight of almost 30%, 15 December 2025. https://pharmaceutical-journal.com/article/news/investigational-weight-loss-drug-trial-shows-average-reduced-body-weight-of-almost-30