Shedding Weight and Pain: The Promise of Anti-Obesity Medications in RA Save

For years, rheumatologists have championed weight loss as a cornerstone of care for patients with rheumatoid arthritis (RA) and obesity. RA is an independent risk factor for cardiovascular disease (CVD), a leading cause of morbidity and mortality. Obesity not only exacerbates the inflammatory milieu but is also consistently associated with worse disease outcomes and independently increases cardiovascular risk.

With the advent of FDA-approved anti-obesity medications (AOM) such as semaglutide and tirzepatide, a new avenue for managing this challenging patient population has emerged. But how might these drugs impact the trajectory of RA, and are we on the cusp of a paradigm shift?

A retrospective cohort study (Abstract 2259) sheds light on the intersection of obesity and RA. Among 152 RA patients (mean age 58, 90% female) prescribed semaglutide (93.4%) or tirzepatide (6.6%), significant improvements were observed in several domains over one year. Key outcomes included:

• Weight loss: Mean weight reduction of 8% and BMI decrease of 3.4 kg/m².
• Inflammatory markers: CRP and ESR decreased by 27% and 21% respectively
• Pain:  Visual analogue scale (VAS) scores decreased by 15%.
• Lipids: Total cholesterol, LDL, and triglycerides decreased by 18.5%, 17.2%, and 19.1%, respectively.

These findings suggest that AOMs may not only mitigate obesity-related comorbidities but also modulate systemic inflammation and pain, presenting a potentially transformative addition to RA care.

The physiological interplay between obesity, inflammation, and RA offers a compelling rationale for these results. Excess adipose tissue is a reservoir  of pro-inflammatory cytokines such as TNF-α and IL-6, key drivers of RA disease activity. In this cohort, weight loss correlated with reductions in inflammatory markers, suggesting that targeted weight reduction could disrupt this proinflammatory  loop. While composite RA disease activity outcomes were incomplete, the observed trends are promising.

Striking improvements in cardiovascular risk factors further underscore the potential impact. Dyslipidaemia, hypertension and diabetes affected was present in 59.9%, 56.6% and 51.3% of patients at baseline. Reductions in key modifiable drivers of CVD, such as LDL and triglycerides, may translate into meaningful improvements in morbidity and mortality. Pain reduction, evidenced by a 15% improvement in VAS scores, highlights another potential benefit. This improvement is likely derived from both a reduction in mechanical  stress as well as reduced systemic inflammation, suggesting a multifactorial impact of AOMs.

Despite their promise, AOMs are not without challenges.

In this study, 42 participants (27%) discontinued therapy. Gastrointestinal side effects, reported by 15%, led to treatment discontinuation in nearly a quarter of cases. Insurance barriers also accounted for a significant proportion of dropouts (26%), a stark reminder of the need for improved accessibility and advocacy.

Several critical questions remain. Incomplete data on composite RA disease activity scores precludes definitive conclusions about AOM’s effects on remission rates or joint-specific outcomes. Moreover, their influence on the pharmacokinetics or efficacy of disease-modifying antirheumatic drugs (DMARDs) warrants exploration. Could weight loss unmask previously resistant RA, allowing for improved DMARD efficacy? Conversely, might altered metabolic states necessitate adjustments in therapeutic regimens? Could side effects potentially negatively impact adherence to DMARDs?

The integration of AOMs into RA care represents an exciting frontier, offering tantalizing benefits that extend beyond weight loss including improvements in systemic inflammation, cardiovascular risk, and potentially disease control.

The potential to redefine management of RA and obesity is huge. It would be easy to get carried away.

However, these promising preliminary findings also highlight significant challenges of AOMs, including side effects, access issues, and incomplete data. I do believe that AOMs  will herald a transformative shift in RA management, offering a powerful adjunct to conventional therapies, but rigorous research and thoughtful implementation is needed.