GLP-1 Receptor Agonists May Improve Rheumatoid Arthritis Symptoms

Glucagon-like peptide 1 receptor agonists (GLP-1RA) have made waves as treatments for obesity and type 2 diabetes, but a new report suggests they might also have clinical benefits for certain patients with rheumatoid arthritis (RA).

The study, which was published in the American College of Rheumatology’s ACR Open Rheumatology journal, found GLP-1RAs led to improvement in disease activity and a lowering of cardiovascular risk factors in patients with RA who had a body mass index at or above 27.¹ 

Previous research suggests that patients with RA who also have obesity tend to have increased disease activity and inferior treatment outcomes, the authors noted.² That’s particularly notable, they said, because one study of North American patients with RA found more than 3 in 10 patients also had obesity.³ They noted that patients with obesity are “in a chronic proinflammatory state due to the overproduction of inflammatory cytokines and adipocytokines.”¹

That heightened inflammation may in turn worsen RA symptoms and progression, the authors noted. Obesity also has negative implications for cardiovascular health, they said, as does RA itself.

Given the apparent connection between weight and RA, the investigators wanted to see if the new high-profile GLP-1RAs might provide a particular benefit to patients with RA who were also overweight.

The investigators conducted a chart review of health records from a single medical center to identify patients with a BMI of at least 27 who were prescribed either semaglutide (which is sold under the brand name Wegovy when used for weight management) or the dual GLP-1RA and glucose-dependent insulinotropic polypeptide receptor agonist tirzepatide (Mounjaro; Lilly).

The authors identified a total of 173 patients treated between 2018 and 2024 who met the inclusion criteria. An additional 42 patients were identified who had RA and were prescribed a GLP-1RA but did not take it. Those patients were treated as the control group. Assessments took place at 3-month intervals for the first year after the prescription, the authors said.

The authors found that patients who took GLP-1RAs experienced significant benefits compared with the control group. Patients taking the therapy had superior changes in RA disease activity (mean change score –0.03 vs +0.2, P = .03), visual analog scale pain scores (–0.6 cm vs +1.3 cm, P < .001), weight (–4.4 kg vs –1.2 kg, P < .001), total cholesterol values (–10.3 mg/dL vs +0.3 mg/dL, P = .04), and HbA_1c values (–0.3% vs –0.01%, P = .03), the authors said.

The investigators also noted improvements in erythrocyte sedimentation rate, C-reactive protein values, low-density lipoprotein cholesterol levels, and triglyceride values (P < 0.05). They said the cardiovascular benefits of weight loss are well-documented, but they said it may be that the GLP-1RAs have independent effects on cardiovascular risk aside from the indirect effect of sparking weight loss.

Though the study data suggest GLP-1RAs led to significant health benefits for patients, the authors also noted that nearly one-third of the treatment group discontinued GLP-1RA therapy during the study period. Gastrointestinal adverse effects and insurance-related difficulties were the most commonly cited reasons for discontinuing, they said.

“These issues are important to address when prescribing GLP-1RAs because they have the potential to impact patient-related outcomes and markedly limit drug efficacy if target dosing cannot be achieved,” the authors wrote.

The authors added that one notable difference between the treatment group and the control group was a significantly higher proportion of White patients in the treatment group compared with the control group (71% vs 47%). They said this may be a consequence of barriers to care that disproportionately affect Black, Hispanic, and Asian patients. They said future studies of GLP-1RAs in patients with RA should aim to increase cohort diversity.

The authors said they hope their findings spark additional research into how GLP-1RAs affect patients with RA.

“The recent proliferation of GLP-1RAs has had a remarkable impact on the management of obesity, diabetes, and cardiovascular risk in the general population, but the impact of these drugs on patients with RA has, to this point, been poorly studied,” they concluded.

References

1. Kellner DA, Dente E, Tran V, et al. Effect of glucagon-like peptide 1 receptor agonists on patients with rheumatoid arthritis. ACR Open Rheumatol. 2025;7(9):e70103. doi:10.1002/acr2.70103
2. Liu Y, Hazlewood GS, Kaplan GG, Eksteen B, Barnabe C. Impact of obesity on remission and disease activity in rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2017;69(2):157-165. doi:10.1002/acr.22932
3. Colmegna I, Hitchon CA, Bardales MC, Puri L, Bartlett SJ. High rates of obesity and greater associated disability among people with rheumatoid arthritis in Canada. Clin Rheumatol. 2016;35(2):457-460. doi:10.1007/s10067-015-3154-0