Weight loss drug semaglutide may offer relief for knee arthritis pain

In a recent study published in The New England Journal of Medicine, researchers used a 68-week-long, extensive (61 centers across 11 countries), randomized clinical trial to evaluate Semaglutide's pain- and weight-relieving performance in overweight arthritis patients.

A once-weekly 2.4 mg subcutaneous injection of the novel antidiabetic wonder drug was observed to reduce body weight (13.7%) and pain (WOMAC = 41) substantially more than similar placebo dosages (3.2% and 27.5 points, respectively).

Semaglutide consumption almost doubles physical function gains compared to placebo (12.0 versus 6.5 points), further promoting somatic health, weight loss, and healthy aging. Safety was similar between case (Semaglutide) and control (placebo) cohorts.

Together, these findings add yet another feather in Semaglutide's growing cap of notable achievements, underscoring the drug's potential to replace conventional pharmacological interventions not only in treating excessive body weight and diabetes but also associated conditions without added side effects over existing antidiabetic modalities.

Background

Arthritis is an umbrella term for several diseases characterized by painful and often debilitating inflammation in joints and connective tissues between adjoining bones. Osteoarthritis of the knee (OK) is the most common of these conditions, causing patients substantial pain, impaired mobility, and significantly reduced quality of life.

Several risk factors associated with OK genesis and progress have hitherto been identified, with obesity (excessive body weight) highlighted as a major contributing to the disease. High body mass index (BMI) has been shown to increase joint inflammation, exacerbating pain. Studies have elucidated that weight reductions following arthritis onset can noticeably improve pain and stiffness outcomes.

Conventional weight loss clinical interventions have historically helped improve short-term Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Unfortunately, with bariatric surgery representing a notable exception, most conventional weight loss modalities (dietary- and physical activity-based interventions) are found to provide highly patient-specific, short-term weight benefits that rarely persist for more than a few months and may involve significant alternations to patients' daily routines.

Despite almost guaranteeing positive weight loss outcomes, bariatric surgery is an extensively invasive procedure with potential adverse side effects, making it a 'last-case scenario' in severe obesity. Unfortunately, today's prevalent lifestyle (sedentary) and dietary choices (suboptimal diets such as the Western Dietary Pattern) are driving an unprecedented escalation in obesity incidence, underscoring the need for safe, long-lasting, efficient, and non-surgical interventions that both obesity-induces OK pain and addresses excessive body weight.

About the study

The present study leverages a placebo-controlled clinical trial methodology to elucidate the potential application of Semaglutide, a recently developed antidiabetic drug, in treating weight-associated knee osteoarthritis.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist belonging to the incretin mimetic class. The drug has been extensively validated in obese/overweight and diabetic cohorts, with subcutaneous (usually 2.4 mg) injections administered weekly demonstrating generation-defining gains in long-term weight loss and diabetes management at reduced side-effect costs (compared with conventional pharmacological interventions).

The study cohort was derived from the Semaglutide Treatment Effect in People with Obesity (STEP) 9 trial, a multicentre (61 sites across 11 countries) long-term Semaglutide assessment adopting double-anonymized, randomized, placebo-controlled study methodologies. Adult STEP participants (>18) presenting clinically validated OK and reporting WOMAC scores >40 (100-point scale) were included and randomized into cases and controls (2:1 ratio).

Experimental procedures included weekly intervention administrations (2.4 mg Semaglutide and equivalent placebo injections) alongside guidance on physical and dietary interventions that may improve weight- and/or OK outcomes. Outcomes of interest were reductions in BMI, WOMAC pain scores, or stiffness following 68 weeks of consistent intervention.

Study findings

Safety assessments presented statistically similar findings across both cohorts—10.0% of cases and 8.1% of controls reported adverse side effects (the most common being gastrointestinal tract distress). Severe adverse effects (requiring study discontinuation) were reported in 6.7% of cases and 3.0% of controls. These findings demonstrate that Semaglutide substantially outperforms placebos in excessive weight reduction, resulting in a cascade of OK benefits.

Conclusions

The present study provides clinical evidence for the knee arthritis-relieving benefits of Semaglutide compared to conventional pharmacological interventions against excessive BMI and its OK-associated outcomes (primarily pain and stiffness).

Study findings highlight that Semaglutide can achieve more than 10% additional weight loss compared to current non-surgical interventions, resulting in substantial 41.7-point pain reductions in OK patients.

While present, semaglutides' side-effect inducting potential is comparable to conventional modalities. Together, these findings highlight Semaglutide as a safe and efficient means of promoting weight loss and reducing chronic pain in OK patients.

Journal reference:

• Bliddal, H., Bays, H., Czernichow, S., Uddén Hemmingsson, J., Hjelmesæth, J., Hoffmann Morville, T., Koroleva, A., Skov Neergaard, J., Vélez Sánchez, P., Wharton, S., Wizert, A., & Kristensen, L. E. (2024). Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. New England Journal of Medicine (Vol. 391, Issue 17, pp. 1573–1583). doi:10.1056/nejmoa2403664 https://www.nejm.org/doi/full/10.1056/NEJMoa2403664