SGLT2 inhibitors’ potential autoimmune effects are gaining attention, as these drugs, which primarily treat type 2 diabetes, may also lower risks for autoimmune rheumatic diseases (AIRDs), with a key study in South Korea showing an 11% reduced risk compared to sulfonylureas, a finding that matters for healthcare systems worldwide and affects health economics and policy choices.
Context and Background
Autoimmune rheumatic diseases impact millions globally, causing chronic inflammation in joints and tissues, where conditions like rheumatoid arthritis and lupus lead to high costs and a worldwide burden on healthcare. Type 2 diabetes adds further complexity by impacting more than 500 million adults, with cases in Asia potentially hitting 151 million by 2045.
SGLT2 inhibitors work by blocking glucose reabsorption in the kidneys, and drugs such as dapagliflozin and empagliflozin control blood sugar effectively, as trials like EMPA-REG OUTCOME prove heart and kidney gains, while now research points to immune benefits, since these agents cut inflammation markers and ease T-cell activity through actions that happen beyond sugar control.
The BMJ study from 2025 offers strong data, as researchers used South Korea’s health database covering 2012 to 2022 and followed over 2 million adults with type 2 diabetes, including about 552,000 who started SGLT2 inhibitors and over 1.4 million who took sulfonylureas, with teams excluding those with prior AIRDs, matching groups for fairness, and following up for a median of nine months.
Key Analysis and Insights
The autoimmune protection from SGLT2 inhibitors seems real, as the study found incidence rates of 51.90 per 100,000 person-years for SGLT2 users compared to 58.41 for sulfonylurea users, giving a hazard ratio of 0.89 with confidence intervals of 0.81 to 0.98 and a rate difference of -6.50 per 100,000 person-years, and results held in subgroups by age and sex.
Mechanisms explain this trend, since SGLT2 drugs lower cytokines like TNF-α and IL-6, promote anti-inflammatory cells, and show less kidney damage in lupus models from mouse studies, while human trials note drops in C-reactive protein, suggesting direct immune modulation.
| Outcome | SGLT2 Inhibitors (per 100,000 PY) | Sulfonylureas (per 100,000 PY) | Hazard Ratio (95% CI) | Rate Difference (95% CI) |
|---|---|---|---|---|
| All AIRDs | 51.90 | 58.41 | 0.89 (0.81–0.98) | -6.50 (-11.86 to -1.14) |
| Inflammatory Arthritis | – | – | 0.86 (0.77–0.97) | – |
| Connective Tissue Diseases | – | – | 0.95 (0.79–1.14) | – |
Table 1: Key results from the BMJ study. PY means person-years. Data adapted from Hong et al., 2025.
Exploratory work compared SGLT2 to other drugs, finding that versus DPP-4 inhibitors, risk fell 21% with a hazard ratio of 0.79, while comparisons with GLP-1 agonists showed no clear edge due to small samples limiting those findings, yet SGLT2 inhibitors’ autoimmune links still stand out.
Implications and Recommendations
These results link diabetes care to immune health, and for economics, savings could yield from preventing one AIRD case, offsetting the cost of biologic costs. Policy must adapt accordingly, as value-based pricing of biologics would be affected by how HTA agencies review the data. Recommendations include:
- Update guidelines with new trials for at-risk groups.
- Consider tiered pricing to cut costs globally.
- Model economics using real-world data.
Conclusion
The autoimmune risk reduction from SGLT2 inhibitors offers promise, as the 11% drop in AIRD incidence aids diabetes patients and eases global burdens on health systems. More studies are needed though across populations in other regions. Readers should consult the full BMJ paper, linked below.
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