Objective: To evaluate the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and risk of autoimmune rheumatic diseases (AIRDs) in patients with type 2 diabetes (T2D).

Design: A retrospective cohort study.

Setting: Nationwide healthcare data of South Korea between 2010 and 2022.

Participants: 1 784 002 individuals aged≥40 years, with T2D who initiated SGLT2 inhibitors or sulfonylureas.

Main outcome measures: The primary outcome was AIRD, defined using established diagnostic criteria as well as physicians’ clinical judgement. Secondary outcomes were individual types of AIRD, including inflammatory arthritis and connective tissue diseases. Genital infections and herpes zoster were employed as positive and negative control outcomes, respectively, to evaluate residual confounding. Hazard ratios (HRs) and rate differences (RDs) per 100 000 person-years were estimated after inverse probability treatment weighting (IPTW) based on propensity score.

Results: After IPTW, 909 048 individuals initiated an SGLT2 inhibitor (mean age 60.9 years; 59.8% male) and 874 954 individuals initiated a sulfonylurea (mean age 60.8 years; 59.4% male). The weighted incidence rate per 100 000 person-years was 56.14 and 64.37 in individuals initiating SGLT2 inhibitors and sulfonylureas, respectively. Over a 9-month median follow-up, SGLT2 inhibitors were associated with a 13% lower risk of incident AIRD compared with sulfonylureas (HR, 0.87 [95% CI, 0.79 to 0.96]; RD, -8.23 [-14.10 to -2.36]). Findings were overall consistent among subgroups stratified by age, sex, individual drug of SGLT2 inhibitors, baseline cardiovascular disease, and obesity status. The HRs for the control outcomes were 2.71 (2.65 to 2.77) for genital infections, and 1.03 (1.01 to 1.05) for herpes zoster.

Conclusions: In this large cohort of individuals with T2D, SGLT2 inhibitors were associated with a 13% lower risk of AIRD compared with sulfonylureas. These results suggest that SGLT2 inhibitors may contribute to reducing the risk of autoimmune diseases, and if replicated, could lead to a potential new therapeutic approach in the treatment of these diseases.