Hydroxychloroquine dose-dependently reduces the risk of incident diabetes in primary Sjögren syndrome patients on glucocorticoids: a nationwide population-based cohort study

Hydroxychloroquine (HCQ) is commonly used to treat Sjögren syndrome (SS). Glucocorticoids, which are commonly applied for managing primary SS (pSS), can disrupt glucose metabolism and increase diabetes mellitus (DM) risk. HCQ reduces DM risk in systemic lupus erythematosus and rheumatoid arthritis. This study aimed to investigate the relationship between HCQ and glucocorticoids in the incidence of new-onset diabetes in pSS. This nationwide population-based cohort study identified patients diagnosed with pSS from the Taiwan’s National Health Insurance Research Database from 2006 to 2015. Multivariate and stratified analyses, Kaplan–Meier method, and Cox proportional hazard regression were used to evaluate DM risk associated with the use of HCQ and glucocorticoid, both individually and in combination. Among pSS patients (4,874 HCQ users and 2,437 HCQ nonusers), 497 patients developed DM over an average follow-up of 4.89 years. Multivariate analysis revealed significantly lower adjusted hazard ratios (aHRs) for DM in HCQ users in the 151–350 cumulative defined daily dose (cDDD) and ≥ 351 cDDD subgroups (0.600, 95% CI: 0.454–0.794 and 0.326, 95% CI: 0.246–0.433, respectively) compared with HCQ nonusers. High-dose glucocorticoids (≥ 151 cDDD) were linked to increased DM risk (aHR: 1.833, 95% CI: 1.410–2.383). However, high-dose HCQ (> 350 cDDD) mitigated this risk, even the risk caused by the use of high-dose glucocorticoids (≥ 151 cDDD) (aHR: 0.632, 95% CI: 0.421–0.948, P < 0.01). Our study demonstrated that HCQ exposure significantly reduces the risk of developing diabetes in patients with pSS. While higher doses of glucocorticoids are associated with an increased diabetes risk, concurrent HCQ use mitigates this risk in a dose-dependent manner.