Aims/IntroductionWe compared the satisfaction levels of patients with type 2 diabetes undergoing combination therapy with lixisenatide (LIX) and basal insulin with that of patients undergoing multiple daily insulin injection (MDI) therapy.Materials and MethodsThe study was a 12‐week open‐label, randomized, multicenter, controlled trial. Participants were Japanese patients with type 2 diabetes receiving MDI for >3 months. Patients were randomly assigned to each treatment cohort: (i) a group that continued MDI (MDI group); and (ii) a group that switched from MDI to combination therapy with LIX and basal insulin (LIX group). The primary outcome was change in Diabetes Treatment Satisfaction Questionnaire scores from baseline to 12 weeks between these two groups. Key secondary outcomes were glycated hemoglobin and body weight changes.ResultsA total of 31 patients were initially enrolled in the study, and 26 of them completed the study. The change in Diabetes Treatment Satisfaction Questionnaire scores in the LIX group was significantly greater compared with that in the MDI group. Mean changes in glycated hemoglobin levels were −0.05 ± 0.37% in the MDI group and 0.04 ± 0.38% in the LIX group (P = 0.36). Mean changes in body weight were +0.6 ± 1.8 kg in the MDI group and −2.5 ± 1.8 kg in the LIX group (P < 0.01).ConclusionsSwitching from MDI to combination therapy with LIX and basal insulin improved satisfaction levels while maintaining glycemic control in Japanese patients with type 2 diabetes.

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin.MethodsIn this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500–750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed.ResultsNinety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m2; HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (− 0.80 ± 0.38% vs. − 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (− 0.51 [− 1.08–0.06]% vs. − 0.58 [− 1.20–0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66–0.62; p < 0.01), the change did not differ significantly between the two groups (− 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 μg/mL vs. 0.01 μg/mL; p < 0.01).ConclusionsRegardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0607-6) contains supplementary material, which is available to authorized users.

Aims/Introduction We compared treatment satisfaction in type 2 diabetes patients taking daily and weekly glucagon‐like peptide‐1 receptor agonists. Materials and Methods The study was a 12‐week, multicenter, open‐label, prospective, randomized, parallel‐group comparison trial. The participants were Japanese patients with type 2 diabetes being administered with the glucagon‐like peptide‐1 receptor agonist, liraglutide, daily for >3 months. Patients were randomly assigned to either continue taking liraglutide once daily (Lira group) or switch to dulaglutide once weekly (Dula group). The primary outcome was the change in the Diabetes Treatment Satisfaction Questionnaire score from baseline to week 12 in the two groups. The secondary outcomes comprised changes in the Diabetes Therapy‐Related Quality of Life score, body mass and glycemic control. Results A total of 33 participants were initially enrolled in the trial, and 31 participants completed the protocol. The change in the Diabetes Treatment Satisfaction Questionnaire score in the Dula group was significantly greater than that in the Lira group (+0.1 ± 4.7 in the Lira group vs +4.9 ± 5.2 in the Dula group; P = 0.013). The change in Diabetes Therapy‐Related Quality of Life score in the Dula group was significantly greater than that in the Lira group (−3.7 ± 6.9 vs +8.9 ± 15.1; P = 0.007). There were no significant differences between groups in the changes in body mass, plasma glucose or glycated hemoglobin. Conclusions Weekly administration of dulaglutide was superior to liraglutide with regard to treatment satisfaction in patients with type 2 diabetes, in the absence of any negative effect on glycemic control.

Aims/Introduction: To identify the coefficient of variation (CV) threshold for unstable glucose variability (GV) and hypoglycemia, and to characterize a patient population with unstable GV and hypoglycemia. Materials and Methods: This was an observational study that enrolled 284 Japanese outpatients with type 2 diabetes who underwent continuous glucose monitoring. The Cpeptide index (CPI = [(fasting serum C-peptide) / (plasma glucose)] 9 100) was used as a marker of endogenous insulin secretion. The CV threshold between stable and unstable GV was defined as the upper limit of the CV distribution in the subgroup of patients who did not receive insulin nor insulin secretagogues (relatively stable GV subgroup, n = 104). The optimal CV range corresponding to time below target range ≥4% was determined for all patients using receiver operating characteristic curve analysis. Various characteristics of patients with unstable GV and hypoglycemia were extracted using multivariate logistic regression analysis. Results: The upper limit of the CV in the relatively stable GV subgroup was 40. The optimal CV range corresponding to time below target range ≥4% was also defined as CV ≥40 (area under the curve 0.85) for all patients. The CPI was an independent risk for CV ≥40 (odds ratio 0.17, 95% confidence interval 0.04-0.50, P < 0.01). The optimal cut-off point for CPI to predict a CV cut-off value of 40 was equivalent to 0.81 (area under the curve 0.80). Conclusions: A CV of 40 discriminates unstable GV and hypoglycemia from stable GV in Japanese outpatients with type 2 diabetes. Impaired insulin secretion might affect the stability of GV.

The effects of dapagliflozin (DAP) and pioglitazone (PIO) on body weight and glycaemic control were compared in patients with type 2 diabetes mellitus. Seventy‐one patients on PIO were either switched to DAP (n = 36) at 5 mg per day or continued on PIO (n = 35). Primary endpoints were superiority of body weight loss and non‐inferiority of HbA1c level after 24 weeks with DAP. Body weight decrease was greater with DAP than with PIO (75.3 ± 14.9 to 71.3 ± 15.1 kg vs. 74.7 ± 13.8 to 75.2 ± 13.9 kg; P < 0.01). Change in the HbA1c level was comparable ( P = 0.64). The level of N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) and urinary albumin : creatinine ratio (ACR) decreased only with DAP (NT‐proBNP, P < 0.01; ACR, P = 0.02), and the change in NT‐proBNP correlated negatively with baseline NT‐proBNP level (ρ = −0.68, P < 0.01) and log‐converted ACR (ρ = −0.35, P < 0.05). DAP promotes body weight loss in type 2 diabetes mellitus and may decrease fluid retention, thus reducing the occurrence of cardiovascular events.

ObjectiveThe aim of this study was to examine the fluctuations in CD4+ T cells, CD8+ T cells, and natural CD4+CD25+FoxP3+T-regulatory (Treg) cells following an oral glucose tolerance test (OGTT) in participants with and those without type 2 diabetes (T2DM).Methods19 Japanese participants with T2DM (DM group) and 21 participants without diabetes (non-DM group) were recruited and underwent a 75-g OGTT. The cell numbers of leukocytes, lymphocytes, and the T cell compartment, such as CD4+, CD8+, and Treg, were calculated for blood samples obtained after an overnight 12 h fast and during a 75-g OGTT at 60 and 120 min.ResultsBefore glucose loading, no differences in the cell numbers of leukocytes, lymphocytes, CD4+, CD8+, and Treg were observed between the DM group and the non-DM group. The proportion of CD8+ was significantly reduced, whereas the proportion of CD4+ was significantly increased, after 120 min of glucose loading in both groups. The proportion of Treg was not affected. Furthermore, a significant positive correlation was observed between the AUC0–120 min of CD8+ and the change in the free fatty acid level following the OGTT (ρ = 0.39, P < 0.05), but not that of glucose or insulin.ConclusionThe proportion of CD4+ T cells was increased and that of CD8+ T cells was reduced after glucose loading in both subjects with and without diabetes. These findings suggest that glucose loading dynamically affects the balance of the circulating T lymphocyte subset, regardless of glucose tolerance.

Aims/Introduction Sodium–glucose cotransporter 2 inhibitors, as well as thiazolidines, suppress nonalcoholic fatty liver disease (NAFLD); however, few comparative studies have been reported. Dapagliflozin has shown non‐inferiority compared with pioglitazone for glycemic control, and superiority regarding weight reduction in patients with type 2 diabetes. We carried out a secondary analysis for the favorable effects of sodium–glucose cotransporter inhibitors for NAFLD. Materials and Methods In this multicenter, open‐label, prospective, randomized, parallel‐group comparison trial, patients taking pioglitazone for ≥12 weeks were randomly switched to dapagliflozin or continued pioglitazone for a further 24 weeks. The fatty liver index (FLI), consisting of body mass index, triglycerides, waist circumference and γ‐glutamyl transpeptidase, was used for the evaluation of NAFLD. Results A total of 53 participants with NAFLD (27 dapagliflozin; 26 pioglitazone) were included in this analysis. FLI decreased significantly in the dapagliflozin group (48.7 ± 23.4 to 42.1 ± 23.9) compared with the pioglitazone group (49.0 ± 26.1 to 51.1 ± 25.8; P < 0.01). Multiple linear regression analysis showed that the changes in FLI had a significantly positive correlation with changes in glycated hemoglobin (P = 0.03) and insulin level (P < 0.01) in the dapagliflozin group. Conclusion Dapagliflozin might be more beneficial than pioglitazone in patients with NAFLD. Improvements in FLI would be closely related to glycemic control.

IntroductionIncretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on glycaemic and weight control, but little evidence has been published for the superiority of semaglutide for glycaemic control in patients after switching from a dipeptidyl peptidase-4 (DPP-4) inhibitor. Therefore, we aim to verify the efficacy of oral semaglutide in patients with T2D being treated with a DPP-4 inhibitor.Methods and analysisThis study is a multicentre, prospective, randomised, open-label, parallel-group trial. In total, 172 participants with T2D who have been treated with a DPP-4 inhibitor for more than 12 weeks and who have a glycated haemoglobin (HbA1c) level of 7.0%–9.9% will be randomised to continue using their existing DPP-4 inhibitor or switch to oral semaglutide for 24 weeks. Biochemical analyses and physical assessment will be performed, and adverse events will be recorded at baseline and at the end of the study. The primary endpoint will be the effect of oral semaglutide on the change in HbA1c. The secondary endpoints will be the mean changes in body weight, abdominal circumference, systolic and diastolic blood pressure (BP), pulse rate, the relationship between improvement of metabolic parameters including HbA1c and patient background characteristics, side effects and other laboratory parameters.Ethics and disseminationThis will be the first study to compare the effects of switching from a DPP-4 inhibitor to oral semaglutide on glycaemic control in patients with T2D. The results will be disseminated in peer-reviewed journals and at scientific conferences. Hokkaido University Certified Review Board (CRB no.1180001) has approved the protocol (no. 020–013).Trial registration numberUMIN000045270 in the University Hospital Medical Information Network; jRCT1011210032 in the Japan Registry of Clinical Trials.