Emerging data at ACR Convergence 2025 highlight the expanding potential of metabolic therapies in rheumatology.
Weight loss achieved through treatment with novel anti-obesity medications appears to significantly lower serum urate levels in patients with gout and baseline hyperuricemia, according to new research presented at ACR Convergence 2025.
The poster presentation detailed analysis of the Mass General Brigham (MCB) electronic health record (EHR) database.
MGB is a not-for-profit, integrated health system based in Greater Boston in the US that operates two academic medical centres – Massachusetts General Hospital and Brigham and Women’s Hospital – as well as specialty and community hospitals, home care, urgent care and a licensed health plan serving Massachusetts and southern New Hampshire.
The researchers identified all patients with gout with baseline hyperuricemia (SU ≥6 mg/dL) who had SU measurements available within three months before and more than three months after starting a novel AOM as part of routine clinical care.
A novel AOM was defined as semaglutide or tirzepatide. Patients with gout were identified using an algorithm with a positive predictive value of 0.9 against the 2015 ACR/EULAR gout classification criteria.
Twenty-two patients were identified as meeting the criteria. The average patient was aged 54.6 years, and 77.3% were male with a mean baseline BMI of 39.3 kg/m². Half of the patients were being treated for obesity while the remaining half received the medication for type 2 diabetes, though most had comorbid obesity.
Over a mean treatment period of 258 days, nearly one-third (31.8%) of patients lost 5–10% of their body weight, 22.7% lost more than 10% and 45.5% lost 5% or less.
The investigators found a strong relationship between weight loss and reductions in serum urate. Each kilogram of weight loss corresponded to a 0.13 mg/dL drop in serum urate, and each one-unit decrease in BMI was associated with a 0.41 mg/dL decline.
Patients who lost more than 10% of their body weight experienced a mean 2.36 mg/dL greater reduction in serum urate compared with those who lost less than 5% (p for trend < 0.001).
“In this retrospective study, novel AOM-induced weight loss was associated with a significant reduction in SU among patients with gout with baseline hyperuricemia,” the researchers concluded.
“These results suggest that novel AOM may be a powerful multi-purpose medication for the many patients with gout and obesity and call for larger-scale studies to test this hypothesis.”
GLP-1 receptor agonists and SGLT2 inhibitors were hot topics at ACR this year with a number of presentations delving into the role they might play in the management of rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis and osteoarthritis (OA).
Among the presentations was a poster from Dr Shreya Sakthivel, chief resident, Internal Medicine at the Anne Arundel Medical Center and principal investigator for the study, Impact of SGLT2 Inhibitors and GLP-1 Agonists on RA Flares in Patients on DMARD Therapy: A Retrospective Study.
The retrospective cohort analysis using real-world data examined the association between SGLT2 or GLP-1 use and RA flare outcomes in DMARD-treated patients using real-world retrospective data.
The study, which analysed data from the TriNetX research network between 2019 and 2024, examined adults with RA who had more than 12 months of follow-up after starting DMARD therapy.
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Participants were categorised into three treatment groups: DMARDs alone, DMARDs plus an SGLT2 inhibitor and DMARDs plus a GLP-1 receptor agonist. Patients with other inflammatory arthritides, malignancy, transplant history, pregnancy, combined SGLT2 and GLP-1 use or prolonged corticosteroid exposure were excluded.
RA flares were assessed using a composite index incorporating oral prednisone use, intravenous (IV) methylprednisolone or joint injections, elevated C-reactive protein (CRP ≥10 mg/L) or erythrocyte sedimentation rate (ESR ≥20 mm/h) and DMARD escalation.
At baseline, the GLP-1 group had the highest mean number of concurrent DMARDs (2.51) but the lowest count at follow-up (1.31), suggesting greater therapeutic adjustment over time.
ESR and CRP levels were most elevated in the SGLT2 inhibitor group prior to treatment initiation. When comparing flare burden scores, statistically significant differences were observed between groups. The DMARD-only group showed a mean flare burden of 1.12 ± 2.44, compared to 1.71 ± 3.79 in the GLP-1 group and 1.30 ± 1.78 in the SGLT2 inhibitor group.
The researchers concluded that the use of SGLT2i was associated with a significant reduction in RA flares.
GLP-1 showed a non-significant trend toward flare reduction, though they noted that this may reflect higher baseline RA severity which may influence the trend.
They said the findings support the need for further prospective studies to validate the anti-inflammatory potential of SGLT2 inhibitors in RA and further explore the effect of GLP-1 on RA flare.
“These findings highlight a growing recognition of the intersection between metabolic health and rheumatic disease,” said Dr Sakthivel.
“GLP-1 therapies, in particular, are emerging as dual-action agents that not only improve cardiometabolic risk factors but may also influence disease activity and long-term outcomes for patients with autoimmune and inflammatory conditions.”
ACR Convergence 2025 was held in Chicago from 24-29 October.
