Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55–75] years) were older than those in the continuation group (64 [53–71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented.

(1) Background: As no study has evaluated the risk factors contributing to the development of type 2 diabetes according to body weight mass (BMI) categories in a large cohort and over a long period in a Japanese population, we aimed to assess them in 46,001 Japanese individuals; (2) Methods: This long-term retrospective cohort study included individuals who participated in a medical health checkup program at Panasonic Corporation from 2008 to 2018. In total, 3,208 participants developed type 2 diabetes. The BMI at 2008 were divided into 3 groups: BMI < 22 kg/m², 22 ≤ BMI < 25 kg/m², and BMI ≥ 25 kg/m² to evaluate the risk factors for type 2 diabetes; (3) Results: Cox regression analyses revealed that the significant risk factors were age, BMI, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, current smoking status, and alcohol consumption in populations with BMI ≥ 25.0 kg/m². The risk factors in the population with 22 ≤ BMI < 25 kg/m² were identical to that of BMI ≥ 25.0 kg/m² excluding systolic blood pressure, low-density lipoprotein cholesterol, and skipping breakfast. However, in the population with BMI < 22.0 kg/m², no association was found as to BMI, SBP, LDL cholesterol level, and triglycerides; (4) Conclusions: The risk factors for developing diabetes were quite different between the population with BMI < 22 kg/m² and the population with 22 ≤ BMI < 25 kg/m² or BMI ≥ 25 kg/m² in a Japanese population.

Aim: This study aimed to investigate how sarcopenia and nutritional risk influence all-cause mortality among older individuals with type 2 diabetes mellitus. Methods: In view of the presence of sarcopenia, defined according to the Asian Working Group for Sarcopenia (AWGS) criteria, and nutritional risk, as determined by the Geriatric Nutritional Risk Index (GNRI), a total of 396 participants were divided into four distinct groups (group 1: no nutritional risk and no sarcopenia, n = 306; group 2: nutritional risk and no sarcopenia, n = 32; group 3: no nutritional risk and sarcopenia, n = 36; and group 4: nutritional risk and sarcopenia, n = 22). Mortality risk was assessed through time-to-event analysis using Cox regression. Results: Throughout the 86-month median follow-up, 31 participants died. Compared to group 1, hazard ratios (HRs) for mortality of groups 2, 3, and 4 were 9.08 (95% confidence interval (95% CI), 2.44–33.8), 9.08 (95% CI: 2.44–33.8), and 14.0 (95% CI: 4.62–42.4), respectively. The risk of death was significantly higher in groups 2, 3, and 4 compared to group 1. Additionally, group 4 had a significantly higher risk of death than group 3. However, no significant difference in mortality risk was observed between groups 3 and 4 when compared to group 2. Conclusions: Coexistence of nutritional risk and sarcopenia was linked to an increased risk of mortality across older individuals with type 2 diabetes mellitus. There was no significant difference in mortality between individuals presenting or not presenting with sarcopenia within the nutritional risk group; therefore, greater attention should be directed toward malnutrition.

Background: Type 2 diabetes (T2D) has been linked to impairments in skeletal muscle performance, encompassing reductions in both muscle strength and muscle quality. While malnutrition is a known modifiable factor contributing to muscle quality deterioration, its specific relationship with the Geriatric Nutritional Risk Index (GNRI) in T2D remains underexplored. Using data from 743 participants in the KAMOGAWA-A cohort, this cross-sectional study evaluated the association between muscle quality and GNRI in individuals with type 2 diabetes. Methods: Muscle quality was defined as handgrip strength divided by arm lean mass. GNRI was calculated using serum albumin and body mass index. Multiple linear regression models were used to assess associations between GNRI and muscle quality. To account for BMI-related dependency in muscle quality measurements, we derived BMI-adjusted GNRI residuals and performed the same regression analysis to evaluate the stability of the observed relationship beyond BMI-induced confounding. Results: In the overall population, GNRI was inversely associated with muscle quality (β = −0.17, p < 0.001). Conversely, residual GNRI demonstrated a significant positive association with muscle quality (β = 0.13, p < 0.001), especially among men, individuals under 65 years of age, and across all BMI categories. Stratified analyses suggested that the strength and direction of associations varied by age, sex, and glycemic control status. Conclusions: The GNRI showed an inverse correlation with muscle quality, whereas residual GNRI showed a consistent positive relationship. These findings suggest that improving nutritional status may support muscle function in T2D, but BMI confounds the interpretation of GNRI in this context.

Aims: To investigate the long‐term renal effects of tofogliflozin, with the shortest half‐life among sodium–glucose cotransporter 2 inhibitors, in real‐world clinical practice. Materials and methods: We retrospectively enrolled patients with type 2 diabetes mellitus treated at three affiliated hospitals between January 2015 and May 2024. The primary outcome was the change in estimated glomerular filtration rate from baseline to 72 months. After inverse probability of treatment weighting, linear mixed‐effects models were used to compare estimated glomerular filtration rate changes between the tofogliflozin and non‐tofogliflozin groups. As a sensitivity analysis, multiple imputation was performed to address missing baseline urinary albumin‐to‐creatinine ratio data. Secondary outcomes included estimated glomerular filtration rate slopes, changes in glycated hemoglobin and body weight at 72 months, and changes in urinary albumin‐to‐creatinine ratio at 48 months. Results: Among 598 participants (tofogliflozin, n = 245; non‐tofogliflozin, n = 353), estimated glomerular filtration rate decline was significantly slower in the tofogliflozin group than in the non‐tofogliflozin group ( P < 0.001). At 72 months, the least squares mean estimated glomerular filtration rate change was −4.51 and −10.64 mL/min/1.73 m ² , respectively (between‐group difference: 6.14 mL/min/1.73 m ² ). Significant between‐group differences were observed in estimated glomerular filtration rate slope, glycated hemoglobin, and body weight, but not in urinary albumin‐to‐creatinine ratio. Renal findings were consistent in the multiple imputation sensitivity analysis. Conclusions: Real‐world clinical data over 72 months suggested that tofogliflozin may slow estimated glomerular filtration rate decline.