Hydroxychloroquine Lowers Risk of New-Onset Diabetes in Primary Sjögren Syndrome: Study

A new study published in the journal of Arthritis Research & Therapy showed that when combined with high-dose glucocorticoid treatment, hydroxychloroquine (HCQ) dramatically lowers the incidence of new-onset diabetes in individuals with primary Sjögren syndrome (pSS).

The autoimmune condition known as primary Sjögren syndrome (pSS) is typified by lymphocytic infiltration of the exocrine glands, resulting in symptoms including dry mouth and eyes. A variety of pharmaceutical medicines are used in the treatment plan to manage symptoms and slow the course of the illness. Originally prescribed as an antimalarial medication, hydroxychloroquine has been used extensively to treat autoimmune diseases such rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

HCQ is advised in pSS to treat systemic active illness, exhaustion, and inflammatory musculoskeletal discomfort. It can also be used as a steroid-sparing medication. Beyond just helping people with SLE or RA manage their symptoms, HCQ has been shown to lower their chance of developing diabetic mellitus (DM). Thus, this study was set to look at how glucocorticoids and HCQ relate to the incidence of new-onset diabetes in pSS.

The patients with pSS were selected from the Taiwanese National Health Insurance Research Database between 2006 and 2015 for this countrywide population-based cohort research. The DM risk linked to the use of HCQ and glucocorticoids, both alone and together, was assessed using multivariate and stratified analyses, the Kaplan–Meier technique, and Cox proportional hazard regression.

Over the course of an average follow-up of 4.89 years, 497 individuals (4,874 HCQ users and 2,437 HCQ nonusers) with pSS developed DM. In comparison to HCQ nonusers, multivariate analysis showed that HCQ users in the 151–350 cumulative defined daily dose (cDDD) and ≥ 351 cDDD categories had substantially decreased adjusted hazard ratios (aHRs) for DM (0.600, 95% CI: 0.454–0.794 and 0.326, 95% CI: 0.246–0.433, respectively).

A higher incidence of diabetes mellitus was associated with high-dose glucocorticoids (≥ 151 cDDD) (aHR: 1.833, 95% CI: 1.410–2.383). Even the risk associated with using high-dose glucocorticoids (≥ 151 cDDD) was reduced by high-dose HCQ (> 350 cDDD) (aHR: 0.632, 95% CI: 0.421–0.948, P < 0.01).

Overall, the findings showed that whereas high doses of glucocorticoids considerably raised the risk of diabetes, high doses of HCQ dramatically decreased the risk of diabetes in pSS patients. However, the risk of diabetes brought on by the use of high dosages of glucocorticoids may be reduced if large doses of HCQ are used concurrently. 

Reference;

Chen, W.-S., Hsu, H.-C., Lin, T.-M., Chang, Y.-S., Lin, Y.-C., Kuo, T.-T., Shen, Y.-C., Chen, S.-C., Chen, J.-H., Lee, H.-Y., & Chang, C.-C. (2025). Hydroxychloroquine dose-dependently reduces the risk of incident diabetes in primary Sjögren syndrome patients on glucocorticoids: a nationwide population-based cohort study. Arthritis Research & Therapy, 27(1), 88. https://doi.org/10.1186/s13075-025-03542-7