Castro Domínguez Francisco

Osteoarthritis is a degenerative joint disease that commonly affects weight-bearing joints such as the knees and hips. Although multiple factors contribute to its progression—age, genetics, prior injury—one key modifiable risk factor stands out: excess body weight.

Each pound of extra weight increases the mechanical load on joints, accelerating cartilage wear and exacerbating pain, stiffness, and functional limitations. Beyond mechanical stress, surplus adipose tissue contributes to "metaflammation," a state of low-grade, chronic inflammation linked to increased production of inflammatory mediators by fat cells. This inflammatory environment can worsen osteoarthritis severity, making effective weight management a cornerstone of comprehensive osteoarthritis care.

As obesity rates rise, so does the urgency to find sustainable, evidence-based strategies for long-term weight reduction. Lifestyle interventions—balanced nutrition, exercise, and physical therapy—remain foundational. However, advances in pharmacotherapy have significantly bolstered our therapeutic arsenal. Two injectable medications, semaglutide and tirzepatide, have shown remarkable efficacy in promoting substantial weight loss, thereby potentially reducing the mechanical and inflammatory burden on osteoarthritis in joints.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that enhances satiety, reduces appetite, and slows gastric emptying. Initially approved at lower doses for type 2 diabetes management, semaglutide is now also approved in a higher dose formulation by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for chronic weight management in adults with obesity or overweight and related conditions. By helping patients achieve an average weight loss of around 15%, semaglutide can alleviate joint load and may reduce metaflammation, potentially improving OA symptoms.

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. This unique "twincretin" approach yields even more pronounced metabolic benefits and appetite suppression than GLP-1 agonists alone. After its initial approval for type 2 diabetes, tirzepatide has now also been approved by the FDA and EMA for chronic weight management. Clinical trials indicate that tirzepatide can achieve weight reductions of 20% or more offering potentially greater relief of both the mechanical stresses and inflammatory load associated with OA.

Both drugs improve glycemic control, blood pressure, and lipid profiles. These benefits support overall metabolic health, further reducing risk factors that may compound OA severity.

Scientific literature explains that excess body weight intensifies OA through two main pathways:

Mechanical overload:

More weight translates to higher forces on the knees, hips, and spine. This increases wear on cartilage and can accelerate joint damage. Reducing body weight lessens stress on the joints, often resulting in reduced pain and improved mobility.

Metaflammation:

Adipose tissue secretes inflammatory cytokines and adipokines that contribute to a state of low-grade inflammation throughout the body. This metaflammation can exacerbate OA symptoms and joint degeneration. Effective weight loss, as seen with semaglutide and tirzepatide, may help lower this inflammatory burden, potentially improving joint health and slowing OA progression.

Side effects

Gastrointestinal side effects such as nausea, vomiting, and diarrhea—are common with both medications, particularly during initial dosing. Slow dose escalation and professional guidance can mitigate these issues. Both semaglutide and tirzepatide are considered relatively safe, with long-term safety data continuing to accumulate.