Semaglutide Reduces Knee Osteoarthritis Pain in People With Obesity

Henning Bliddal, MD, MSci

Credit: The Parker Institute

Weekly injections of semaglutide 2.4 mg resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis (KOA) than placebo in people with obesity and KOA.¹

"Obesity-related knee osteoarthritis is a progressive condition that can lead to pain and stiffness of the knee and impair critical daily functions such as walking or moving around. The risk of developing the condition is more than four times higher in people with obesity. Weight reduction along with physical activity is often a recommended approach to managing painful symptoms, but adherence can be challenging," lead investigator Henning Bliddal, MD, MSci., The Parker Institute, Copenhagen University Hospital, Denmark, said in a statement.¹ "There is a significant need for non-surgical and sustainable treatment options for those living with obesity-related osteoarthritis. The STEP 9 trial aimed to provide rigorous evidence as to how semaglutide may help these people."

Bliddal and colleagues conducted the 68-week, double-blind, randomized, placebo-controlled STEP 9 trial (NCT05064735) at 61 sites in 11 countries. The trial enrolled a total of 407 participants (81.6% women) with a mean age of 56 years, a mean BMI of 40.3, and a mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of 70.9.¹

The investigators found that the mean change in body weight from baseline to week 68 was −13.7% with semaglutide (95% CI, -12.3 to -8.6) compared with −3.2% with placebo (P <.001). At the same time point, the mean change in WOMAC pain score at week 68 was −41.7 points with semaglutide (95% C(, -20.0 to -8.3) compared with −27.5 points with placebo (P <.001), and the improvement in 36-Item Short Form Survey (SF-36v2) physical-function score was 12.0 points with semaglutide (95% CI, 3.1-8.0) compared with 6.5 points with placebo (P <.001).¹

In terms of safety, both groups had a similar incidence of serious adverse events (AEs). Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the semaglutide group and in 3.0% of the placebo group, with gastrointestinal disorders as the most common reason for discontinuation.

"Obesity is a complex metabolic disease associated with multiple co-morbid conditions, including knee osteoarthritis," Anna Windle, PhD, Senior Vice President, Clinical Development, Medical and Regulatory Affairs, Novo Nordisk, added.² "The STEP 9 results are encouraging and provide important information about the effect of semaglutide, a glucagon-like peptide-1 receptor agonist, on knee osteoarthritis outcomes in people with obesity. We look forward to working with regulatory authorities on next steps based on these findings."

Although only FDA-approved for treating adults with type 2 diabetes (T2D) and reducing cardiovascular risk in these individuals, semaglutide is racking up a body of evidence supporting its use in a wide variety of indications.³ Novo Nordisk also just announced headline results from the first part of the ongoing phase 3 ESSENCE trial of once-weekly subcutaneous semaglutide 2.4 mg in adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis.⁴

The data show that, at week 72, 37% of people treated with semaglutide 2.4 mg achieved improvement in liver fibrosis with no worsening of steatohepatitis compared to 22.5% on placebo. Additionally, 62.9% of people treated with semaglutide 2.4 mg achieved resolution of steatohepatitis with no worsening of liver fibrosis compared to 34.1% on placebo. Of note, semaglutide 2.4 mg was well-tolerated with a safety profile similar to previous semaglutide 2.4 mg trials.⁴

REFERENCES

1. Bliddel H, Bays H, Czernichow S, et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N Engl J Med 2024;391:1573-1583. doi: 10.1056/NEJMoa2403664

2. STEP 9 results, published in NEJM, demonstrated semaglutide reduced knee osteoarthritis-related pain in people with obesity. News release. Novo Nordisk. October 30, 2024. https://www.prnewswire.com/news-releases/step-9-results-published-in-nejm-demonstrated-semaglutide-reduced-knee-osteoarthritis-related-pain-in-people-with-obesity-302292063.html

3. Ozempic FDA Approval History. Webpage. https://www.drugs.com/history/ozempic.html

4. Novo Nordisk. Novo Nordisk A/S: Semaglutide 2.4 mg demonstrates superior improvement in both liver fibrosis and MASH resolution in the ESSENCE trial. November 1, 2024. Accessed November 1, 2024. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=171971