SGLT-2 inhibitors may protect against autoimmune rheumatic diseases
- 31-10-2025
- Autoinflammatory Diseases
- Editor's Choice
- News
medwireNews: Sodium-glucose cotransporter (SGLT)-2 inhibitors, originally developed as antidiabetic drugs, appear to lower the risk for autoimmune rheumatic diseases in individuals with type 2 diabetes compared with sulfonylureas, reveals a large-scale population-based South Korean study.
The research, published by The BMJ, indicates that the likelihood of developing an autoimmune rheumatic disease is reduced by 11% with the initiation of SGLT-2 inhibitors, compared with sulfonylureas, with the incidence of inflammatory arthritis lowered by 14%.
“SGLT-2 inhibitors may contribute to reducing the risk of autoimmune diseases,” say Ju-Young Shin (Sungkyunkwan University, Republic of Korea), and colleagues. However, with the study also pointing to some adverse outcomes with the drugs, they add that “this potential benefit should be carefully weighed against known adverse events and concerns about tolerability.”
Discussing the findings in an accompanying editorial, Derin Karacabeyli and Diane Lacaille, both from the University of British Columbia in Vancouver, Canada, write: “While in isolation this study is unlikely to change practice, it is the first full length publication to suggest that SGLT-2 inhibitors reduce the risk of autoimmune rheumatic diseases.
“This intriguing finding, seen after only nine months of median follow-up, suggests a clinically relevant immunomodulatory effect that warrants replication in different populations.”
SGLT-2 inhibitors, such as dapagliflozin, empagliflozin, and canagliflozin, are “considered one of the drug repurposing candidates for autoimmune disease,” comment the researchers, due to their immunomodulatory properties, including the reduction of pro-inflammatory markers, the modulation of immune cell activity, and improvements in oxidative stress.
To test this theory, the team leveraged data from a South Korean nationwide healthcare database. They identified 2,032,157 individuals aged at least 18 years with a diagnosis of type 2 diabetes who received an SGLT-2 inhibitor or a sulfonylurea (as a control group) between September 2014 and December 2022.
Of these individuals, 552,065 were new users of SGLT-2 inhibitors and 1,480,092 of sulfonylureas. None of the patients had a diagnosis of autoimmune rheumatic disease prior to the study.
Following propensity score weighting, 1,030,088 initiators of SGLT-2 inhibitors and 1,002,069 individuals who started on sulfonylureas were included in the analysis. The participants had a mean age of 58.5 years, and 60% were male.
Over a median follow-up of 9.1 months, the absolute incidence of autoimmune rheumatic diseases was low, with 790 initiators of SGLT-2 inhibitors and 840 individuals who started on sulfonylureas receiving a diagnosis.
This equated to an incidence rate of autoimmune rheumatic diseases of 51.9 and 58.4 per 100,000 person–years, respectively, with a significant rate difference in favor of SGLT-2 use of 6.5 or a hazard ratio (HR) of 0.89. Looking at individual autoimmune rheumatic diseases, HRs were a significant 0.86 for inflammatory arthritis but a nonsignificant 0.95 for connective tissue disease.
The results for autoimmune rheumatic diseases overall were consistent across subgroups, including when stratifying patients by age, sex, type of SGLT-2 inhibitor, baseline cardiovascular disease, and obesity.
However, the researchers note that the initiation of SGLT-2 inhibitors was associated with a significantly higher risk for developing genital infections compared with sulfonylureas (HR=2.78), as well as herpes zoster (HR=1.03).
They also recognize the study’s limitations, including its observational nature, leading to the possibility of unmeasured confounding, and a relatively high rate of treatment discontinuation, although, as they point out, treatment discontinuation is also common in clinical practice,” making our findings representative of expected outcomes in such settings.”
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