Adults with type 2 diabetes who used sodium-glucose cotransporter-2 inhibitors developed fewer new cases of autoimmune rheumatic diseases than those on sulfonylureas, according to a population-based cohort study published in The BMJ. 

During a median follow-up of 9 months, the weighted incidence rate per 100,000 person-years was 51.9 among sodium-glucose cotransporter-2 inhibitor users and 58.4 among sulfonylurea users, yielding a hazard ratio of 0.89 and a rate difference of −6.5 per 100,000 person-years. The reduction was driven mainly by a lower risk of inflammatory arthritis (hazard ratio [HR], 0.86), whereas no significant difference was observed for connective tissue diseases (HR, 0.95).

Using the South Korean National Health Insurance Service database, which covers 98% of the population, researchers analyzed data from 2,032,157 adults aged 18 years or older with type 2 diabetes from 2012 to 2022.  Among them, 552,065 initiated sodium-glucose cotransporter-2 (SGLT-2) inhibitors and 1,480,092 initiated sulfonylureas. After applying inverse probability treatment weighting based on propensity scores to adjust for confounders such as comorbidities, medication use, and metabolic factors, 1,030,088 SGLT-2 inhibitor users and 1,002,069 sulfonylurea users were included in the weighted cohort (mean age, 58.5 years; 60% men).

The primary outcome—autoimmune rheumatic disease—was defined through diagnostic codes and registration in the national Rare Intractable Disease Program, ensuring diagnostic accuracy. Subgroup analyses showed consistent findings across age, sex, obesity status, baseline cardiovascular disease, and type of SGLT-2 inhibitor. Sensitivity analyses, including intention-to-treat and propensity score matching models, confirmed the robustness of the results.

For control outcomes, SGLT-2 inhibitors were associated with a higher risk of genital infections (HR, 2.78) but not herpes zoster (HR, 1.03), supporting internal validity. “Accumulating mechanistic evidence suggests that GLP-1 receptor agonists may exert anti-inflammatory or immunomodulatory effects, highlighting the need for further studies to assess their potential role in the treatment of autoimmune rheumatic diseases,” wrote Bin Hong, doctoral student, of the School of Pharmacy, Sungkyunkwan University, Republic of Korea, and colleagues.

This study was funded by the Ministry of Food and Drug Safety in South Korea; Dr. Ju-Young Shin received additional governmental and industry grants, and all other researchers reported no competing interests.

Source: The BMJ