SGLT2 Inhibitors Linked to Modestly Lower Risk of Autoimmune Rheumatic Diseases in Type 2 Diabetes Patients
A large population-based Korean study has found that patients with type 2 diabetes starting on SGLT2 inhibitors had a slightly lower risk of developing autoimmune rheumatic diseases compared with those treated with sulfonylureas.
Published in The BMJ, the retrospective analysis covered data from more than two million adults with type 2 diabetes between 2012 and 2022, drawn from South Korea’s National Health Insurance Service database.
Over a median follow-up period of nine months, researchers observed a weighted incidence rate of 51.9 cases per 100,000 person-years among those using SGLT2 inhibitors versus 58.4 cases per 100,000 person-years for sulfonylurea users — corresponding to a hazard ratio (HR) of 0.89 (95% CI 0.81–0.98).
When broken down by disease category, the reduced risk was significant for inflammatory arthritis (HR 0.86), but not for connective tissue diseases (HR 0.95).
“The results suggest that the anti-inflammatory and immunomodulatory effects of SGLT2 inhibitors, as suggested in previous studies, are clinically significant,” said lead author Ju-Young Shin, PhD, of Sungkyunkwan University in Seoul.
Interestingly, the benefit appeared stronger among participants with a body mass index below 25 (HR 0.78), suggesting that SGLT2 inhibitors may have direct immunological effects independent of their metabolic benefits.
In an accompanying editorial, Dr. Derin Karacabeyli and Dr. Diane Lacaille of the University of British Columbia noted that while the findings may not immediately influence clinical practice, they point toward a “clinically relevant immunomodulatory effect” that deserves replication in other populations and longer-term follow-up studies.
The researchers also noted that while autoimmune rheumatic diseases remain relatively rare, the findings are biologically plausible. Preclinical studies have shown SGLT2 inhibitors can reduce secretion of pro-inflammatory cytokines and induce macrophage shifts from pro-inflammatory (M1) to anti-inflammatory (M2) subtypes.
Still, the authors of the editorial cautioned that the absolute risk reduction was small, estimating that more than 15,000 adults would need to be treated with an SGLT2 inhibitor instead of a sulfonylurea for one year to prevent a single case of autoimmune rheumatic disease.
They added that further research could explore whether GLP-1 receptor agonists — another major class of antidiabetic drugs — might confer similar immunomodulatory effects, especially as prescribing trends shift away from sulfonylureas.
The study excluded canagliflozin (Invokana) due to lack of reimbursement during the study period and adjusted for multiple confounders, including comorbidities, concurrent medications, and health behaviors.
While observational in nature, the findings add to growing evidence that SGLT2 inhibitors may play a broader role beyond glycemic control, potentially offering subtle protection against inflammation-related diseases.
