[Health Focus] “Next-generation obesity treatment Retatrutide reduces knee osteoarthritis pain”

Clinical trial results showed that retatrutide, which is being developed by American pharmaceutical company Eli Lilly as a next-generation obesity treatment, reduces pain caused by knee osteoarthritis while reducing weight.

In an analysis of 1,019 participants in the phase 3 clinical trial, the retatrutide group had a greater reduction in body weight and pain scores than the placebo group. In particular, in about two-thirds of the 9 mg and 12 mg treatment groups, the knee pain score decreased by more than 50%.

On the 9th, Professor Thomas Schnitzer's team at Northwestern University announced in the medical journal New England Journal of Medicine (NEJM) that they had confirmed these results in two phase 3 clinical trials of Retatrutide on 1,019 adults who were overweight or obese and had knee osteoarthritis pain.

Professor Schnitzer, the corresponding author, said: "These results show that people who are overweight and have osteoarthritis are likely to experience meaningful reductions in knee pain if they lose significant weight with Retatrutide treatment."

Retatrutide is a triple agonist that simultaneously activates glucagon-like peptide-1 (GLP-1), insulinotropic peptide (GIP) receptors, and glucagon receptors.

Eli Lilly is developing Retatrutide as a next-generation obesity treatment injection that goes one step further than the existing Wigobi (semaglutide) and Maunjaro (tirzepatide), and is attracting attention as it showed a stronger weight loss effect than existing treatments in phase 3 clinical trials.

Two phase 3 clinical trials led by the research team involved 1,019 adults without diabetes who were overweight (BMI 27 or more) or obese and had painful knee osteoarthritis.

In one clinical trial (TRIUMPH-4) that lasted 68 weeks, 445 people, and in another clinical trial (TRIUMPH-1-OA) that lasted 80 weeks, 574 people were randomly assigned to a drug or placebo group and received retatrutide or placebo by subcutaneous injection once a week.

Knee pain before and after drug administration was assessed using the Western Ontario-McMaster University Osteoarthritis Index (WOMAC). The pain score ranges from 0 to 10, with higher scores indicating more severe pain.

As a result, in the TRIUMPH-4 trial, at week 68, body weight decreased by an average of 20.0% in the retatrutide 9 mg administration group and 23.7% in the 12 mg administration group. The weight loss rate in the placebo group was 4.6%.

In the TRIUMPH-1-OA trial, at week 80, body weight decreased by 17.5% in the 4 mg administration group, 22.9% in the 9 mg administration group, and 24.8% in the 12 mg administration group, a greater reduction than the placebo group (4.3%).

In a combined analysis of the two clinical trials, 69.6% of participants in the 9 mg Retatrutide group and 63.2% of participants in the 12 mg group had their knee pain score reduced by more than 50% at 68 weeks. In the placebo group, it was 37.8%.

The WOMAC physical function score, which reflects the ability to perform daily physical activities such as walking or climbing stairs, also improved by more than half in the drug administration group (63.5-64.6%) than in the placebo group (33.1%).

Citing previous research, the research team explained that when weight is lost, the load on the knee joint decreases, and that if you lose 1 pound (about 0.45 kg) of body weight, the load on the knee decreases by about 4 pounds (about 1.8 kg).

The research team also suggested the possibility that reducing fatty tissue could contribute to pain relief by reducing systemic inflammatory mediators. However, it was revealed that the specific mechanism by which GLP-1 class drugs reduce pain has not yet been fully revealed.

He added, “This clinical trial was conducted on patients with knee osteoarthritis who are overweight or obese, so it is unknown whether it is effective in patients with normal weight as well,” adding that follow-up research is needed to determine whether Retatrutide changes the progression of the joint disease itself.

◆ Source: New England Journal of Medicine, Thomas Schnitzer et al., "Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity", https://doi.org/10.1056/NEJMoa2610676