PurposeThere are very few epidemiological studies on chronic urticaria (CU). We aimed to investigate the prevalence of CU and to depict demographics and medication patterns for the disease in a nationwide population-based study.MethodsData on urticaria (L50 of the International Classification of Diseases, 10th revision) from 2010 to 2014 were obtained from the Korean Health Insurance Review and Assessment Service. Algorithms designed to evaluate prescription drug claims for antihistamines were applied to identify CU.ResultsThe crude prevalence of CU was 2,256.5 per 100,000 person-years and tended to increase every year. The age-standardized prevalence of CU was significantly higher in females than in males (2,466.8 vs 1,819.2 per 100,000 person-years, P<0.001). Age-specific prevalence was highest for older adults over the age of 65 years and lowest for ages 10-29 years. The median duration of CU was 591 days, and symptoms lasted for at least 1 year in 61.9% of patients. Gastrointestinal disease was the most common comorbidity in adults, whereas allergic rhinitis and common cold were more prevalent in children with CU. Around a third of CU patients were taking antihistamine treatment alone, and 70% were treated with both antihistamines and systemic corticosteroids. Cyclosporine was prescribed for 0.02% of CU patients.ConclusionsThe present study outlines recent longitudinal epidemiological data on the prevalence of CU in Korea. In light of limitations on the use of claims data, including no specific disease code for CU and a possible discordance between drug claims and the presence of urticaria symptoms, further investigations are necessary to describe the exact epidemiologic profile of CU patients.

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Background. Sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs whose anti-inflammatory properties have recently become useful in tackling metabolic syndromes in chronic inflammatory diseases, including diabetes and obesity. We investigated whether empagliflozin (SGLT2 inhibitor) and gemigliptin (DPP-4 inhibitor) improve inflammatory responses in macrophages, identified signalling pathways responsible for these effects, and studied whether the effects can be augmented with dual empagliflozin and gemigliptin therapy. Methods. RAW 264.7 macrophages were first stimulated with lipopolysaccharide (LPS), then cotreated with empagliflozin, gemigliptin, or empagliflozin plus gemigliptin. We conducted quantitative RT-PCR (qRT-PCR) to determine the most effective anti-inflammatory doses without cytotoxicity. We performed ELISA and qRT-PCR for inflammatory cytokines and chemokines and flow cytometry for CD80, the M1 macrophage surface marker, to evaluate the anti-inflammatory effects of empagliflozin and gemigliptin. NF-κB, MAPK, and JAK2/STAT signalling pathways were examined via Western blotting to elucidate the molecular mechanisms of anti-inflammation. Results. LPS-stimulated CD80+ M1 macrophages were suppressed by coincubation with empagliflozin, gemigliptin, and empagliflozin plus gemigliptin, respectively. Empagliflozin and gemigliptin (individually and combined) inhibited prostaglandin E2 (PGE2) release and COX-2, iNOS gene expression in LPS-stimulated RAW 264.7 macrophages. These three treatments also attenuated the secretion and mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, and proinflammatory chemokines, such as CCL3, CCL4, CCL5, and CXCL10. All of them blocked NF-κB, JNK, and STAT1/3 phosphorylation through IKKα/β, MKK4/7, and JAK2 signalling. Conclusions. Our study demonstrated the anti-inflammatory effects of empagliflozin and gemigliptin via IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 pathway downregulation in macrophages. In all cases, combined empagliflozin and gemigliptin treatment showed greater anti-inflammatory properties.

Aim To examine the real‐world cardiovascular effectiveness and safety associated with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor compared with dipeptidyl peptidase‐4 (DPP‐4) inhibitor treatment in older adults with type 2 diabetes. Materials and Methods In this retrospective cohort study, older adults with type 2 diabetes (aged ≥65 years) were identified in the Korean National Health Insurance Service database from September 2014 to December 2016. In total, 408 506 new users of an SGLT2 inhibitor or DPP‐4 inhibitor were propensity score matched. Cox regression was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for outcomes of interest: hospitalization for heart failure (HHF), all‐cause death, myocardial infarction, stroke, diabetic ketoacidosis (DKA), bone fracture, severe hypoglycaemia, genital infection and urinary tract infection (UTI). Results Compared with DPP‐4 inhibitors, new users of SGLT2 inhibitors had a lower risk of HHF (HR 0.86; 95% CI 0.76‐0.97), all‐cause death (HR 0.85; 95% CI 0.75‐0.98) and stroke (HR 0.86; 95% CI 0.77‐0.97), but a similar risk of myocardial infarction (HR 0.95; 95% CI 0.77‐1.19). The risks of DKA, bone fracture and severe hypoglycaemia were similar between both groups, although genital infection (HR 2.44; 95% CI 2.22‐2.67) and UTI (HR 1.05; 95% CI 1.00‐21.11) were more frequent among new users of SGLT2 inhibitors compared with DPP‐4 inhibitors. Conclusion Our findings suggest that initiation of SGLT2 inhibitors offers cardiovascular disease protection and can be used safely in older adults with type 2 diabetes.

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