Sodium-glucose cotransporter-2 (SGLT-2) inhibitors used to treat type 2 diabetes are associated with an 11% lower risk of autoimmune rheumatic diseases, such as rheumatoid arthritis and lupus, compared with another group of diabetes drugs called sulfonylureas, finds a study from South Korea published by The BMJ today.
Autoimmune rheumatic diseases occur when the body mistakenly attacks its own healthy tissues, leading to inflammation and damage to joints, skin, muscles, and other organs. Common conditions include rheumatoid arthritis, lupus, and scleroderma.
Previous studies have shown that SGLT-2 inhibitors can inhibit the body's immune response, but whether these effects are clinically meaningful remains unclear.
To address this, researchers used the Korea National Health Insurance Service database to analyse 2,032,157 adults with type 2 diabetes (average age 59; 60% men) who started taking either an SGLT-2 inhibitor or a sulfonylurea from 2012 to 2022.
Potentially influential factors such as age, sex, income level, existing conditions and drug treatments, healthcare use, and lifestyle factors were taken into account, and two control outcomes (genital infections and herpes zoster) were also included to assess the risk of bias.
A total of 790 participants taking SGLT-2 inhibitors and 840 participants taking sulfonylureas were newly diagnosed with autoimmune rheumatic disease.
Over an average follow-up period of 9 months, SGLT-2 inhibitors were associated with an 11% lower risk of autoimmune rheumatic diseases compared with sulfonylureas, with incidence rates per 100,000 person years of 52 and 58, respectively.
Findings were largely consistent among subgroups analysed by age, sex, type of SGLT-2 inhibitor, baseline cardiovascular disease, and obesity status. The results for control outcomes also suggested that bias was likely minimal.
This is an observational study so no firm conclusions can be drawn about cause and effect, and the authors acknowledge that follow-up was relatively short, and other unmeasured factors may have affected the results.
However, they say this was a large study that applied rigorous methods to nationwide data, and, as such, these results suggest that SGLT-2 inhibitors may contribute to reducing the risk of autoimmune diseases.
"However, this potential benefit should be carefully weighed against known adverse events and concerns about tolerability," they write. "Replication in other populations and settings, as well as studies in patients with existing autoimmune rheumatic diseases, are warranted to confirm and extend these observations."
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, say researchers from Canada in a linked editorial.
Although this intriguing finding warrants replication in different populations, this study "sets a foundation for future research and provides preliminary evidence to support an additional reason to use an SGLT-2 inhibitor over a sulfonylurea for the management of type 2 diabetes," they conclude.
