Weekly Semaglutide Injection Reduces Knee Osteoarthritis Pain

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In a recent clinical trial, weekly semaglutide demonstrated promise as a nonsurgical, nonopioid intervention for reducing knee osteoarthritis pain.

Once-weekly injectable semaglutide significantly reduced both body weight and knee osteoarthritis pain compared to placebo, according to research published in the New England Journal of Medicine.1

Knee pain / yodiyim - stock.adobe.com

Knee pain / yodiyim - stock.adobe.com

Osteoarthritis of the knee, the most prevalent form of osteoarthritis, results in chronic pain, decreased mobility, disability, and impaired quality of life. Obesity-related knee osteoarthritis arises from a combination of elevated mechanical stress on weight-bearing joints, metabolic dysfunction, and obesity-induced inflammation.

Even a modest weight gain of 10 pounds can increase knee pressure by 30 to 60 pounds per step,2 but weight reduction has been demonstrated to alleviate symptoms of knee osteoarthritis, including pain. Despite this, there remains an unmet need for weight-management medications capable of facilitating nonsurgical, sustained weight reduction and pain reduction in individuals with the dual conditions.

About STEP 9

Trial Name: Research Study Looking at How Well Semaglutide Works in People Suffering From Obesity and Knee Osteoarthritis

Clinicaltrials.gov Identifier: NCT05064735

Sponsor: Novo Nordisk A/S

Summary: This study will look at participants body weight from the start to the end of the study. It will also look at how much pain participants have in participants knee from the start to the end of the study and how this affects participants daily life.

The Semaglutide Treatment Effect in People with Obesity (STEP) 9 trial (NCT05064735) assessed the efficacy of a 2.4-mg dose of semaglutide as an adjunct to lifestyle modifications in reducing body weight and knee osteoarthritis-related pain among participants with obesity.

The STEP 9 trial was a 68-week, double-blind, randomized, placebo-controlled trial conducted at 61 sites across 11 countries. Participants were adults aged 18 years or older with obesity and a clinically and radiologically confirmed diagnosis of knee osteoarthritis with at least moderate pain.

For eligibility and efficacy assessments, the trial utilized the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) numerical rating scale with a 24-hour recall period. WOMAC scores were normalized and expressed on a scale of 0 to 100, with higher scores reflecting worse outcomes.

Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous injections of semaglutide or a visually identical placebo for 68 weeks. After that, there was a 7-week follow-up period during which neither semaglutide nor placebo was administered. Throughout the trial, participants in both groups were counseled on a reduced-calorie diet and physical activity.

The primary end points were the percentage change in body weight and the change in WOMAC pain score from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2, which is a scale of 0 to 100 with higher scores indicating greater well-being.

READ MORE: Ketamine Improved Chronic Pain for Patients with Cancer Following Surgery

Between October 2021 and March 2022, a total of 407 participants were enrolled in the study and randomly assigned to receive either semaglutide (n = 271) or placebo (n = 136).

The study population was predominantly female (81.6%), with a mean age of 56 years, a mean BMI of 40.3, and a mean WOMAC pain score of 70.9. Semaglutide resulted in a statistically significant mean weight loss of 13.7% compared to 3.2% with placebo (P < .001).

At week 68, participants treated with semaglutide experienced a significant mean reduction in WOMAC pain score of 41.7 points compared to 27.5 points in the placebo group (P < .001). Additionally, a higher percentage of participants treated with semaglutide achieved at least 5% (87.0 vs 29.2%) and 10% (70.4% vs 9.2%) weight loss compared to placebo.

Semaglutide also resulted in a significantly greater improvement in SF-36 physical function score from baseline, with a mean change of 12.0 points in participants treated with semaglutide compared with 6.5 points in participants treated with placebo (P < .001).

The incidence of serious adverse events was comparable between the semaglutide and placebo groups. A total of 6.7% participants in the semaglutide group discontinued treatment due to adverse events, most commonly gastrointestinal disorders, compared to 3.0% in the placebo group.

Currently, semaglutide is FDA-approved for weight loss, type 2 diabetes, and reducing cardiovascular risk.3 However, current study findings suggest it could also be an effective solution to reduce moderate-to-severe pain associated with knee osteoarthritis. Pharmacists should counsel patients on the potential benefits and risks of semaglutide, including its off-label use for nonsurgical, nonopioid pain management, and advise them to consult with their health care providers for personalized recommendations.

READ MORE: Nonopioid Pain Management

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References
1. Bliddal H, Bays H, Czernichow S, et al. Once-Weekly semaglutide in persons with obesity and knee osteoarthritis. N Engl J Med. 2024;391(17):1573-1583. doi:10.1056/NEJMoa2403664
2. Role of body weight in osteoarthritis. Fact sheet. Johns Hopkins Arthritis Center. Accessed November 1, 2024. https://www.hopkinsarthritis.org/patient-corner/disease-management/role-of-body-weight-in-osteoarthritis/
3. Semaglutide. Fact sheet. National Library of Medicine. Accessed November 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK603723/
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