Changes in Treatment Satisfaction Over 3 Years in Patients With Type 2 Diabetes After Initiating Second-line Treatment.

CONTEXT: J-DISCOVER is a prospective observational cohort study aiming to understand the current management of patients with early-stage type 2 diabetes mellitus (T2DM) in Japan, enrolling patients initiating second-line treatment. OBJECTIVE: The current analysis examined the change in treatment satisfaction during the study period and factors affecting this change among patients in J-DISCOVER. METHODS: We used data from the J-DISCOVER study, in which 1798 patients with T2DM aged ≥ 20 years were enrolled from 142 sites across Japan. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). RESULTS: The mean DTSQ treatment satisfaction score increased from 25.9 points at baseline to 27.3 points at 6 months, which was maintained through 36 months. Among the baseline characteristics examined, higher baseline DTSQ treatment satisfaction scores (P < 0.0001), older age (≥ 75 vs < 65 years, P = 0.0096), living alone (P = 0.0356), and type of facility (clinics vs hospitals, P = 0.0044) had a significantly negative impact on the changes in DTSQ treatment satisfaction scores. Improvement in mean glycated hemoglobin (HbA1c) from baseline (7.7%) to 36 months (7.1%) was associated with positive changes in the DTSQ treatment satisfaction score (P = 0.0003). CONCLUSION: Changes in DTSQ treatment satisfaction scores were related to HbA1c improvement, suggesting that the management strategy was appropriately planned for each patient. The results also suggest that the availability of social support for patients with T2DM who are elderly or living alone may be an important factor affecting treatment satisfaction, adherence, and clinical outcomes.

Factors associated with the glucose-lowering efficacy of sitagliptin in Japanese patients with type 2 diabetes mellitus: Pooled analysis of Japanese clinical trials.

AIMS/INTRODUCTION: To explore the factors associated with the glucose-lowering efficacy of sitagliptin treatment in Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This was a post-hoc analysis of pooled data from seven sitagliptin phase II and III clinical studies carried out in Japan. All studies were double-blind, randomized, placebo-controlled, parallel-group and of 12-week duration. The analysis population consisted of 1,075 type 2 diabetes mellitus patients. In two of the trials, sitagliptin 50 mg and/or 100 mg daily were used as monotherapy; in five others, sitagliptin 50 mg daily was used as add-on treatment to ongoing pioglitazone, glimepiride, metformin, voglibose or glinides. Efficacy (reduction in hemoglobin A1c [HbA1c]) was evaluated in 12 sets of subgroups defined by demographic, glycemic, pancreatic ß-cell function and insulin resistance parameters. An analysis of covariance model was used to evaluate the interaction between each parameter and efficacy. RESULTS: Sitagliptin consistently provided a clinically meaningful reduction in HbA1c relative to placebo across all subgroups. Within subgroups, a greater absolute HbA1c reduction was associated with higher baseline HbA1c, fasting plasma glucose and 2-h post-meal glucose. Lower ß-cell function, represented by homeostatic model assessment of ß-cell function and insulinogenic index, was also associated with greater HbA1c reduction. In contrast, age, sex, body mass index, duration of type 2 diabetes mellitus and insulin resistance-related parameters did not interact with HbA1c changes. CONCLUSIONS: Sitagliptin treatment was associated with clinically meaningful improvement in glycemic control in all subgroups of Japanese patients with type 2 diabetes mellitus that were evaluated. Higher baseline glycemic status and lower baseline ß-cell function were identified as factors associated with greater HbA1c reduction after sitagliptin treatment.

Baseline Characteristics of Patients with Type 2 Diabetes Initiating Second-Line Treatment in Japan: Findings from the J-DISCOVER Study.

INTRODUCTION: J-DISCOVER aims to research the treatment reality of Japanese patients with type 2 diabetes mellitus who begin second-line treatment. Here we report baseline characteristics and factors associated with selection of second-line treatment. METHODS: J-DISCOVER is a prospective, observational, multicenter, cohort study in patients with type 2 diabetes (aged ≥ 20 years) beginning second-line treatment after first-line oral monotherapy. Baseline characteristics and treatment patterns were descriptively summarized. Logistic regression models were used to identify factors associated with specific second-line treatments. RESULTS: A total of 1806 patients (mean age 61.7 years) were enrolled between September 2014 and December 2015. Mean ± standard deviation of baseline glycated hemoglobin (HbA1c) and body mass index (BMI) were 7.7 ± 1.3% and 25.5 ± 4.6 kg/m2, respectively. The most prescribed medication as first-line treatment was dipeptidyl peptidase 4 inhibitors (53.7% of patients) followed by biguanides (21.4%), sulfonylureas (7.2%), and alpha-glucosidase inhibitors (6.8%). Second-line treatments included dipeptidyl peptidase 4 inhibitors (31.0%), biguanides (27.9%), sodium-glucose cotransporter 2 inhibitors (12.2%), and sulfonylureas (10.9%). First- and second-line treatments had different modes of action in 76.3% of patients. Those receiving first-line dipeptidyl peptidase 4 inhibitors were more likely to receive second-line biguanides and vice versa. Selection of second-line treatment was also associated with age, BMI, HbA1c, and renal function. CONCLUSIONS: This study showed the treatment reality and factors associated with choice of second-line treatment in Japanese patients with type 2 diabetes mellitus. The choice of second-line treatment was associated with age, BMI, HbA1c, renal function, and the mode of action of the first-line treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02226822.

Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial.

Background: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers. Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and <80% predicted were randomized to single oral dose of imidafenacin 0.1 mg, imidafenacin 0.2 mg, or placebo. Results: Maximum change in FEV1 with both doses of imidafenacin significantly improved from baseline to 24 hrs after administration when compared with a placebo. Area under the curve in FEV1 during 24 hrs after administration with 0.2 mg, but not 0.1 mg dose, was significantly improved when compared with a placebo, and the improvement was significantly based on dose-dependent manners. Plasma imidafenacin level was positively correlated with change in FEV1. All subjects with both doses of imidafenacin completed without moderate nor severe adverse events. Conclusion: A single oral dose of imidafenacin 0.1 mg or imidafenacin 0.2 mg may contribute to the improvement of pulmonary function with excellent safety and tolerability in patients with COPD. Trial registration: JapicCTI-121760 (Japan Pharmaceutical Information Center - Clinical Trials Information [JapicCTI]; http://www.clinicaltrials.jp/user/cteSearch_e.jsp).

Effects of yogurt supplemented with fish oil on plasma lipid and glucose concentrations, and liver lipid contents in mice.

The aim of this study is to clarify the effects of yogurt supplemented with fish oil on plasma lipid and glucose concentrations, and hepatic lipid contents in mice. Male Crlj:CD-1 (ICR) mice were fed five experimental diets for 12 weeks. The experimental diets were as follows: without yogurt and fish oil (control diet); 10% (w/w) yogurt without fish oil [10% FO(-)]; 10% yogurt with fish oil [10% FO(+)]; 30% yogurt without fish oil [30% FO(-)]; 30% yogurt with fish oil [30% FO(+)]. Plasma triacylglycerol concentrations in the 10% FO(+) and 30% FO(-) groups were significantly lower than that in the control diet group (p < 0.05 and p < 0.05, respectively). Plasma total cholesterol and phospholipid concentrations were significantly lower in the 30% FO(+) group than in the control diet group (p < 0.005). Concentrations tended to be lower with supplementation with fish oil. Plasma glucose concentrations in the 10% FO(+) and 30% FO(+) groups were significantly lower than those in the control diet group (p < 0.005 and p < 0.01, respectively). Hepatic triacylglycerol and total cholesterol contents in the 30% FO(+) group were significantly lower than those in the control diet group (p < 0.05 and p < 0.005, respectively). These results suggest that plasma triacylglycerol and glucose concentrations are effectively decreased by supplementation of yogurt with fish oil.

Rationale and Design for the J-DISCOVER Study: DISCOVERing the Treatment Reality of Type 2 Diabetes in a Real-World Setting in Japan-A Protocol.

INTRODUCTION: It is estimated that 642 million adults worldwide will have diabetes by 2040, with 80-90% of these having type 2 diabetes mellitus (T2DM). While many new antidiabetic agents have been introduced in recent years, approximately 40% of T2DM patients still fail to achieve the recommended target HbA1c of < 7.0%. Furthermore, many patients with T2DM in Japan are treated by practitioners other than diabetes specialists; therefore, the exact treatment patterns of T2DM in Japan are difficult to quantify. AIMS: J-DISCOVER aims to address the lack of data on the management of T2DM by providing real-world data on disease management patterns and associated outcomes in a large number of Japanese T2DM patients who are initiating second-line therapy. DESIGN AND SETTING: Part of the global DISCOVER study program, J-DISCOVER will follow 2000 T2DM patients recruited from 141 sites across Japan who are aged ≥ 20 years. Recruitment began in September 2014 and follow-up will end in December 2018. The primary objective is to describe the long-term disease management patterns and clinical evolution of patients with T2DM inadequately controlled with a first-line antidiabetic therapy who initiate a second-line antidiabetic treatment. We will assess the associations between treatment patterns, including the line of antidiabetic medication used, as well as clinical and patient-reported outcomes. The primary endpoint is the mean change in HbA1c between baseline and at 6, 12, 24, and 36 months in the overall population and for patients receiving each class of second-line antidiabetic treatment. PLANNED OUTPUTS: A peer-reviewed publication reporting real-world results and implications for clinical practice. CONCLUSION: By enrolling and following a large number of patients with T2DM across Japan, J-DISCOVER is expected to provide important real-world clinical data for the development of future T2DM treatment guidelines. FUNDING: AstraZeneca K.K. and Ono Pharmaceutical Co., Ltd., Osaka Japan. CLINICAL TRIAL REGISTRATION: NCT02226822.