越坂 理也

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.

BACKGROUND AND AIMS: Early prevention of chronic kidney disease is critical. We aimed to identify predictive risk factors for early-stage renal dysfunction. METHODS AND RESULTS: This retrospective study analyzed specific health checkup data from the general Japanese population. We included 1385 adults who underwent a specific health checkup in 2013 and 2019 and had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 in 2013. The composite endpoint was the progression of renal dysfunction for 6 years, including doubling of serum creatinine levels, ≥30 % decline in eGFR, and ≥30 % increase in the urine albumin-to-creatinine ratio (UACR) for individuals with UACR ≥30 mg/gCre at baseline or progression to ≥30 mg/gCre for those with UACR <30 mg/gCre at baseline. Participants were categorized into groups with and without progression of renal dysfunction. Univariate analysis of health checkup data and questionnaire data collected in 2013 was conducted, followed by multiple logistic regression analyses. Significant between-group differences were observed in age, body weight, body mass index (BMI), waist circumference, medication for hypertension and hyperlipidemia, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, diabetes, glycated hemoglobin (HbA1c), urine glucose qualitative, UACR, urine protein-to-creatinine ratio, current smoking, weight gain, and walking habits. Logistic regression analysis showed that BMI (odds ratio [95 % confidence interval]: 1.14 [1.07-1.24], P < 0.001), HbA1c (1.57 [1.24-1.98], P < 0.001), and walking habits (0.51 [0.33-0.80], P = 0.003) were significantly associated with renal dysfunction progression. CONCLUSIONS: Higher BMI and HbA1c and lower walking habits were associated with early-stage renal dysfunction, even in the general population.

BACKGROUND AND AIM: Werner syndrome (WS) is an autosomal recessive, adult-onset, progeroid syndrome caused by WRN mutations. As refractory skin ulcers significantly affect the quality of life of patients with WS, this study identified ulcer risk factors and assessed prevention methods. METHODS: We analyzed the data of 51 patients with WS enrolled in the Japanese Werner Syndrome Registry between 2016 and 2022. A cross-sectional analysis was performed to determine the association with skin ulcers at baseline. Statistical analyses were conducted, including Welch's and Pearson's chi-square tests. Age was adjusted using a logistic regression model. RESULTS: The mean patient age was 48.8±7.6 years, and 66.7% of patients presented with skin ulcers. Univariate analysis showed that patients with skin ulcers were older than those without ulcers. Systolic blood pressure (SBP) was higher in patients with skin ulcers. Patients without skin ulcers received metformin and pioglitazone treatment significantly more often than those with ulcers. Logistic regression analysis adjusted for age showed that higher SBP remained a significant risk factor for skin ulcers. Patients administered pioglitazone had lower ulcer morbidity. CONCLUSIONS: Age and SBP are risk factors for skin ulcers in patients with WS. Moreover, pioglitazone treatment may prevent skin ulcers.