Metformin Use Was Associated With Reduced Risk of Incidental Sjögren's Syndrome in Patients With Type 2 Diabetes: A Population-Based Cohort Study

Abstract

Purpose: Previous studies have shown that metformin exhibits an anti-inflammatory effect and may decrease the risk of incidental diabetes. But the effect of metformin on incidental Sjögren's syndrome is unknown. The aim of the study was to examine the association between metformin exposure and Sjögren's syndrome in diabetic patients.Methods: The dataset in this retrospective cohort study was obtained from the National Health Insurance Research Database (2000–2013) in Taiwan. In total, 15,098 type 2 diabetic patients under metformin treatment and an equivalent number without metformin treatment matched for comparison were included. The primary endpoint was the incidence of Sjogren's syndrome. Univariate and multivariate Cox proportional hazards models were used for data analysis. A subgroup analysis and sensitivity test were also performed.Results: The incidence rate of Sjögren's syndrome in non-metformin controls was 40.83 per 100,000 person-years and 16.82 per 100,000 person-years in metformin users. The adjusted hazard ratio (aHR) in diabetic patients under metformin treatment was 0.46 (95% CI, 0.23 to 0.92). In subgroup analysis, men had a lower risk of developing Sjögren's syndrome than women [aHR = 0.15, 95% CI = (0.05, 0.41)]. After prescribing metformin to type 2 diabetic patients aged 60 years or more, those patients had a lower risk of developing Sjögren's syndrome [aHR = 0.34, 95% CI = (0.12, 0.96)].Conclusion: In this large population-based cohort study, metformin exposure was associated with a reduced risk of developing Sjögren's syndrome in type 2 diabetic patients.

Metformin-induced activation of Ca2+ signaling prevents immune infiltration/pathology in Sjogren’s syndrome-prone mouse models

“…As current therapies have limited success in pSS patients, we started evaluating with FDA-approved drugs to see if they can reverse Sjogren’s Syndrome symptoms in mice. Studies have shown that metformin can be used as a treatment for different autoimmune diseases, due to its immunoregulation ability to decrease inflammation [ 13 ]. To further investigate the effects of Metformin on the progression of Sjogren’s syndrome, we gathered 16 IL-14α Tg 6-month-old female mice and divided them into 2 groups, one was the control group where we fed them saline in a daily basis, the treatment group was fed metformin orally daily at a concentration of 5 mg/kg of body weight.…”

“…Other studies have also suggested that metformin actions go further, such as germinal center formation, macrophage polarization, cytokine production, etc, thereby making metformin a candidate for treatment for immune-mediated diseases [ 11 ]. Similarly, metformin has been shown to reduce salivary gland inflammation and decreased in pSS incidences were observed in patients taking metformin [ 12 , 13 ], suggesting that it can help Sjögren’s patients, but the mechanism is not known.…”

Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology

“…AMPK activation, relevant to SjD, inhibits mammalian target of rapamycin (mTOR) which affects cell growth, survival and proliferation and regulates T cell differentiation 50. We and others have shown that metformin, through mTOR inhibition, might improve SjD 51 52. Thus, motifs bound in SSA− SjD might provide some insight into the functional relevance of our antigenic targets.…”

Association between a History of herpes zoster and the risk of Sjögren’s syndrome: a nationwide, population-based, case–control study

“…Low percentage of patients with SS had dDM and lower risk between herpes zoster exposure and SS in DM patients. The result can be explained by metformin is regarded as the first-line therapy of type 2 DM and reduce the risk of developing SS in patients with DM through anti-inflammatory effect, furthermore, it has been considered as the treatment strategy for SS in the manner of enhancing the immunomodulatory response 37 38. Another finding is low percentage of patients with SS had tumours and metastatic solid tumour and lower risk between herpes zoster exposure and SS in tumours patients.…”