GLP-1 Drugs Reduce Rheumatoid Arthritis Symptoms Save

Patients with rheumatoid arthritis (RA) who used GLP-1 receptor agonists had less disease activity and improved cardiovascular biomarkers, a small retrospective study indicated.

Among 173 RA patients with overweight or obesity who were prescribed GLP-1 agonists and actually took them, 32% showed improvement in RA disease activity after 1 year, compared with 17% of 42 patients who were also prescribed the drugs but never started them, according to Veena Ranganath, MD, MS, of the University of California Los Angeles (UCLA), and colleagues.

Although the difference fell short of statistical significance (P=0.16), there was a significant difference in scores for disease activity, the group reported in ACR Open Rheumatology. With disease activity categorized on a scale of 0 to 3 (remission to severe), the group averages changed by -0.03 points for those using GLP-1 agonists versus +0.21 for non-users (P=0.03). Self-reported pain also declined by an average 0.6 points on the standard 0-10 scale, versus an increase of 1.3 points among the controls.

Those weren't the only changes seen with the drugs. Not only did patients lose weight as expected -- an average of 4.4 kg from baseline -- but triglyceride and low-density lipoprotein (LDL) cholesterol levels also declined significantly. Markers of systemic inflammation including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) also improved with GLP-1 drugs.

"Our study is among the first to assess the effects of GLP- 1 [receptor agonists] on patients with RA, and our findings suggest that they may beneficially impact RA care in several important ways," Ranganath and colleagues wrote. "Further study in the form of prospective trials is needed to better characterize their benefits and risks in this patient population."

hat RA and metabolic function are interrelated isn't a new suggestion. Just the fact that RA is well known to convey markedly increased risk for cardiovascular disease stands as testament. Overweight is also common in patients with RA and other rheumatologic conditions, and management guidelines have long recommended weight loss. Now that GLP-1 agonists are a prominent treatment for overweight and obesity, researchers have begun looking at how patients with rheumatologic diseases respond to these products. Just a few months ago, a group reported that GLP-1 drugs seemed to benefit patients with fibromyalgia, with less pain and fatigue and reduced usage of opioid analgesics.

For the current study, Ranganath and colleagues reviewed records for all patients treated for RA at UCLA from 2018 to 2024, focusing on those with body mass index (BMI) values of at least 27 who received prescriptions for either semaglutide (Wegovy, Ozempic, Rybelsus) or tirzepatide (Mounjaro, Zepbound). Pharmacy records indicated whether these individuals actually had the prescriptions filled. The date for the first such prescription was set as baseline for outcome parameters.

Mean patient age was about 58; somewhat more of the GLP-1-user group were women (90% vs 79%), and significantly more were white (71% vs 47%). Time since RA onset was longer in the user group (mean 12.1 years vs 9.8), and BMI values averaged 37.1 among users versus 35.3 for non-users. Diabetes and hypertension were also more prevalent among users. RA disease activity trended higher among users, with 28% showing moderate or severe symptoms, compared 14% of the non-user group. By the same token, non-users were more often in remission at baseline (29% vs 15%).

Just under 40% of both groups showed no change in RA disease activity during the 1-year study period. As noted earlier, more of the GLP-1 users showed improvement, and consequently more of the non-user group showed worsened disease (46% vs 29%). Ranganath and colleagues also tracked changes in RA medications as a surrogate for disease activity; no significant differences were seen between user and non-user groups, with 33% of both having escalations, and slightly more of the non-users having de-escalations (16% vs 7%).

Changes from baseline in cardiovascular, metabolic, and inflammatory biomarkers among GLP-1 drug users were as follows:

• Triglycerides: -16.4 mg/dL
• LDL cholesterol: -7.3 mg/dL
• HbA1c: -0.3 percentage points
• CRP: -0.6 mg/dL
• ESR: -3.0 mm/hr

These were all numerically greater than corresponding changes for non-users, but often the differences didn't reach statistical significance. Ranganath and colleagues also looked for correlations between weight loss and biomarker trajectories, but these were either weak or nonexistent.

Adverse effects related to GLP-1 drugs were an issue, the researchers found. Fifty of the 173 users discontinued the agents before the 1-year study period was up, most often for gastrointestinal symptoms and "insurance issues."

Limitations to the study included its single-center, retrospective design and small sample size. Data on disease activity were too sparse in many cases to allow quantification by standard methods such as the 28-joint Disease Activity Score; hence, the researchers resorted to categorization (remission, mild, moderate, or severe) with low resolution. Also, it was unclear why the control patients didn't fill their GLP-1 prescriptions, leaving open the possibility of confounding.

Source Reference: Kellner DA, et al "Effect of glucagon-like peptide 1 receptor agonists on patients with rheumatoid arthritis" ACR Open Rheumatol 2025; DOI: 10.1002/acr2.70103.

John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.