石橋 亮一

AIMS: Anti-vascular endothelial growth factor (VEGF) therapy is the standard treatment for diabetic macular oedema (DMO); however, unmet needs remain. This study aimed to assess the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in treating DMO. MATERIALS AND METHODS: This multicentre randomised open-label trial included 60 patients with DMO who were eligible for anti-VEGF therapy. Patients were randomised to receive luseogliflozin or glimepiride. Ranibizumab was administered initially to the target eye, with additional doses per protocol. The number of ranibizumab doses up to week 48, and re-admission rates were evaluated. Fellow eye injections were also assessed. RESULTS: Sixty participants, mostly with diabetic retinopathy and half previously treated with anti-VEGF therapy, were included. SGLT2i and sulfonylurea (SU) groups achieved equivalent glycated haemoglobin, central retinal thickness (CRT), and best-corrected visual acuity improvements. Injection frequency for the target eye was similar between groups (SGLT2i vs. SU: 3.9 ± 0.7 vs. 4.7 ± 0.7 times, p = 0.36). Re-administration rates were decreased significantly after the fourth injection in the SGLT2i group (p = 0.030, hazard ratio: 0.45, 95% confidence interval: 0.22-0.92). Fellow eyes in the SGLT2i group showed significant CRT reduction and fewer injections compared with those in the SU group (1.3 ± 0.6 vs. 3.4 ± 0.8, p = 0.016). CONCLUSIONS: Although the overall number of anti-VEGF injections in the target eye showed no significant difference, some patients responded favourably to SGLT2i and required fewer injections. The reduction in fellow eye injections suggests SGLT2i's efficacy in treating early-stage DMO. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN000033961); Japan Registry of Clinical Trials (jRCTs031180210).

AIMS: To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis. MATERIALS AND METHODS: In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m2 and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, were compared in the sub-analyses. The correlations between changes in each index and VFA were evaluated. RESULTS: At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (-9.24 ± 10.7 vs. -3.45 ± 11.8, p = 0.013), HSI (-1.45 ± 2.32 vs. -0.45 ± 1.87, p = 0.021), NAFLD-LFS (-0.70 ± 1.46 vs. -0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (-0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction (r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively). CONCLUSIONS: Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D.

AIMS/INTRODUCTION: Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. MATERIALS AND METHODS: In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. RESULTS: Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. CONCLUSIONS: The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.