Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT): a multicenter, randomized, open-label, parallel-group study.

INTRODUCTION: This study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported oral therapy (BOT). RESEARCH DESIGN AND METHODS: Changes in mean daily blood glucose level before and after 48-72 hours of add-on or no add-on of dapagliflozin (primary end point) and diabetes-related biochemical variables and major safety variables during the 12 weeks (secondary end point) were evaluated in the multicenter, randomized, two-arm, open-label, parallel-group comparison study. RESULTS: Among 36 participants, 18 were included in the no add-on group and 18 were included in the dapagliflozin add-on group. Age, gender, and body mass index were comparable between the groups. There were no changes in continuous glucose monitoring metrics in the no add-on group. In the dapagliflozin add-on group, mean glucose (183-156 mg/dL, p=0.001), maximum glucose (300-253, p<0.01), and SD glucose (57-45, p<0.05) decreased. Time in range increased (p<0.05), while time above the range decreased in the dapagliflozin add-on group but not in the no add-on group. After 12-week treatment with dapagliflozin add-on, 8-hydroxy-2'-deoxyguanosine (8OHdG), as well as hemoglobin A1c (HbA1c), decreased. CONCLUSIONS: This study showed that the mean daily blood glucose and other daily glucose profiles were amended after 48-72 hours of dapagliflozin add-on in Japanese patients with type 2 diabetes who received BOT. The diabetes-related biochemical variables such as HbA1c and urinary 8OHdG were also obtained during the 12 weeks of dapagliflozin add-on without major adverse events. A preferable 24-hour glucose profile in 'time in ranges' and an improvement in reactive oxygen species by dapagliflozin warrant us to evaluate these benefits in larger clinical studies. TRIAL REGISTRATION NUMBER: UMIN000019457.

Associations between continuous glucose monitoring-derived metrics and arterial stiffness in Japanese patients with type 2 diabetes.

BACKGROUND: Previous studies have suggested that high mean glucose levels and glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear. METHODS: This exploratory cross-sectional study used baseline data from an ongoing prospective, multicenter, observational study with 5 years of follow-up. Study participants included 445 outpatients with type 2 diabetes and no history of apparent cardiovascular disease who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were analyzed using multivariate regression models. RESULTS: In a linear regression model, all CGM-derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM-derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥ 1800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c. CONCLUSIONS: Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.

Efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes.

BACKGROUND: The aim of this study was to investigate the clinical efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes. METHODS: A total of 3,247 subjects treated with sitagliptin were retrospectively recruited. Glucose parameters were collected at baseline, and 1, 3 and 6 months after initiation of sitagliptin. In addition, we explored factors that can be used to predict sitagliptin-induced reduction in HbA1c using linear mixed effect model. Factors associated with hypoglycemic events were examined by logistic analyses. RESULTS: We analyzed the available data of 3,201 subjects (1,287 females). Treatment of sitagliptin significantly reduced HbA1c level from 7.44±1.20% at baseline to 6.73±0.99% at 6 months (P < 0.0001). Linear mixed effect model analyses demonstrated that reduction of HbA1c was associated with higher baseline HbA1c level, younger age, lower BMI and sitagliptin monotherapy. During this study, 82 cases of hypoglycemia were recorded. Logistic analyses indicated that hypoglycemic events were more frequent in female patients, and patients with low BMI, long history of type 2 diabetes, high HbA1c and on combination therapy experienced. Other adverse events were rare and mild. CONCLUSIONS: Sitagliptin is effective for diabetic management and generally well tolerated in Japanese patients with type 2 diabetes. This trial was registered with UMIN (no. 000004121).

Age-specific effectiveness and safety of newly initiated insulin therapy in Japanese patients with uncontrolled diabetes.

INTRODUCTION: One consequence of population aging is an increase in the number of elderly patients with diabetes mellitus. These elderly patients often experience atherosclerotic complications, and diabetes prevention and management are strongly desired to promote health and reduce the financial burden on the healthcare system. In this study, we conducted an age-specific evaluation of the effectiveness and safety of comprehensive management with newly initiated insulin therapy over a 1-year period in elderly (≥65 years) compared with non-elderly (≤64 years) Japanese patients with uncontrolled diabetes [glycated hemoglobin (HbA1c) ≥ 8% for ≥ 3 months]. METHODS: This retrospective single-center cohort study was conducted in Japan. We screened all outpatients with diabetes mellitus who visited the clinic for diabetes treatment between December 2006 and March 2011. Of these patients, 132 with type 2 diabetes who were newly initiated on insulin therapy for continued poor glycemic control and undergoing comprehensive management through self-monitoring of blood glucose (SMBG) were registered to the study. RESULTS: Thirty-two of 132 registered patients were excluded from the analysis. Among the 100 patients (67 non-elderly, 33 elderly) included in the analysis, median age and proportion of male patients was 69 years and 66.7%, respectively, among the elderly, and 52 years and 68.7%, respectively, among the non-elderly patients. After initiation of insulin therapy, median HbA1c levels improved from 9.6% to 7.2% in elderly patients, and from 10.8% to 7.3% in non-elderly patients at baseline and 12 months. Severe hypoglycemic events were not observed in either patient group; however, uncontrolled diabetes was ongoing in 31.8% of non-elderly and 15.4% of elderly patients, and obesity was associated with poor glycemic control. CONCLUSION: Our results indicate that the effectiveness and safety of newly initiated insulin therapy are similar between elderly and non-elderly Japanese patients with uncontrolled diabetes, and highlight the importance of comprehensive management using SMBG to avoid hypoglycemia. Better glycemic control supported by adequate intensive management is required to improve mortality and morbidity.