Sjögren syndrome is an autoimmune condition that is treated chronically with HCQ and glucocorticoids. Although HCQ was found to decrease diabetes risk among patients with systemic lupus erythematosus and rheumatoid arthritis, glucocorticoids disrupt glucose metabolism and create a risk for new-onset diabetes. This research aimed to determine the impact of HCQ and glucocorticoids, either alone or in combination, on the risk of diabetes in pSS patients.
This study analyzed data from Taiwan’s National Health Insurance Research Database, covering the years 2006 to 2015.Patients with pSS were identified and monitored for a mean of 4.89 years. A total of 7,311 patients were enrolled, including 4,874 HCQ users and 2,437 nonusers. Investigators used multivariate analyses, Kaplan–Meier survival curves, and Cox proportional hazard models to examine the effect of HCQ use and glucocorticoid dosing and use on diabetes incidence.
Key Findings
• Among 7,311 pSS patients, 497 developed incident diabetes during follow-up.
• Those with moderate use of HCQ (151–350 cumulative defined daily doses or cDDD) had a 40% lower risk of developing diabetes (adjusted hazard ratio [aHR]: 0.600, 95% CI: 0.454–0.794) than nonusers.
• Those with excessive HCQ intake (≥ 351 cDDD) had a 67% lower risk (aHR: 0.326, 95% CI: 0.246–0.433) than nonusers.
• On the contrary, those with excessive glucocorticoid exposure (≥ 151 cDDD) had an 83% higher risk of developing diabetes (aHR: 1.833, 95% CI: 1.410–2.383).
• But in patients given both high-dose HCQ and high-dose glucocorticoids, there was a 37% decreased risk of diabetes (aHR: 0.632, 95% CI: 0.421–0.948, P < 0.01), suggesting protective effect of HCQ despite glucocorticoid-induced risk of metabolic disturbances.
This national cohort study demonstrated that hydroxychloroquine has a significant protective effect against the development of diabetes in those with primary Sjögren syndrome, and especially if given at higher doses. Even though high-dose glucocorticoids carry a risk of inducing diabetes, this can be prevented by the concomitant use of HCQ, validating its adjunct therapeutic use in autoimmune disease treatment.
Reference:
Chen, WS., Hsu, HC., Lin, TM. et al. Hydroxychloroquine dose-dependently reduces the risk of incident diabetes in primary Sjögren syndrome patients on glucocorticoids: a nationwide population-based cohort study. Arthritis Res Ther 27, 88 (2025). https://doi.org/10.1186/s13075-025-03542-7
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