GLP-1 Receptor Agonists May Reduce Rheumatoid Arthritis Activity and Cardiovascular Risk in People with Obesity

Key Takeaways:

• GLP-1 receptor agonists were linked to reduced rheumatoid arthritis (RA) disease activity and improved cardiovascular risk factors in people with obesity or overweight.
  
• Significant improvements were observed in inflammation markers, weight, and cholesterol levels over 12 months of treatment.
  
• Findings suggest GLP-1RAs could offer dual benefits by addressing both metabolic and inflammatory disease processes in RA.
  
  
  

GLP-1RAs show promise in managing RA and cardiometabolic health

The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) was associated with improvements in both rheumatoid arthritis (RA) disease activity and cardiovascular risk factors among people living with overweight or obesity, according to new research published in ACR Open Rheumatology.

Rheumatoid arthritis frequently coexists with obesity, which is known to exacerbate systemic inflammation, increase disease activity, and reduce response to treatment. Although GLP-1RAs are well established for treating obesity, type 2 diabetes, and for reducing cardiovascular risk, their potential role in inflammatory diseases such as RA has not been clearly defined.

Study overview

Researchers at the University of California, Los Angeles (UCLA) conducted a single-centre, retrospective observational study involving people with RA and a body mass index (BMI) of at least 27 kg/m². Participants were prescribed either semaglutide (oral or subcutaneous) or tirzepatide (subcutaneous) between 2018 and 2024.

Out of 554 screened individuals, 229 met the inclusion criteria. Of these, 173 took the prescribed GLP-1RA and formed the treatment cohort, while 42 individuals served as controls, having been prescribed but not initiating therapy. Participants were evaluated at 3-month intervals for up to 12 months.

Baseline characteristics

Both groups were broadly similar in terms of BMI, RA duration, and the use of conventional, biologic, or targeted synthetic disease-modifying antirheumatic drugs (DMARDs). However, diabetes (49% vs 14%) and hypertension (57% vs 38%) were more common in the treatment group.

The mean baseline BMI was 37.1 kg/m² among those receiving treatment and 35.3 kg/m² among control individuals. A greater proportion of participants in the treatment group were White (71% vs 47%).

Improvements in RA and cardiometabolic outcomes

People who took GLP-1RAs showed significantly greater improvements in several clinical measures compared with those who did not initiate therapy:

• RA disease activity scores: decreased by −0.03 versus an increase of +0.21 in controls (P = .03)
  
• Visual analogue scale (VAS) pain scores: decreased by −0.6 cm versus an increase of +1.3 cm in controls (P < .001)
  
• Weight: reduced by −6.2 kg versus −1.7 kg (P < .001)
  
• Total cholesterol: decreased by −10.3 mg/dL versus +0.3 mg/dL (P = .04)
  
• HbA1c: reduced by −0.4% versus +0.1% (P = .03)
  

Within the treatment group, significant reductions were also noted in inflammatory and lipid parameters, including:

• Erythrocyte sedimentation rate (ESR): −5.4 mm/hr (P = .004)
  
• C-reactive protein (CRP): −0.9 mg/dL (P = .004)
  
• Low-density lipoprotein (LDL) cholesterol: −7.3 mg/dL (P = .002)
  
• Triglycerides: −10.5 mg/dL (P = .004)
  
  
  

Tolerability and limitations

Adverse effects were relatively common, with 29% of participants discontinuing treatment, most frequently due to gastrointestinal symptoms or insurance-related issues.

Sensitivity analyses that accounted for comorbidities and serostatus did not significantly alter the study’s outcomes. However, researchers noted several limitations, including the single-centre, retrospective design, reliance on chart abstraction rather than validated disease activity indices, and the possibility of residual confounding.

Clinical implications

“Going forward, clinicians may consider integrating GLP-1RAs into the treatment regimens for patients with [RA and obesity], not only to target obesity-related complications but also possibly to target the underlying inflammatory disease process,” the authors concluded.

Some study authors disclosed affiliations with biotechnology, pharmaceutical, and medical device companies. A full list of disclosures is available in the original publication.