Network meta-analysis of liraglutide versus dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes in Japanese patients

<p><b>Aims:</b> To determine the comparative efficacy and safety of liraglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors as antidiabetics for Japanese patients with uncontrolled type 2 diabetes (T2DM).</p> <p><b>Methods and materials:</b> We searched for randomized controlled trials (RCTs) evaluating outcomes among Japanese adults with uncontrolled T2DM and including liraglutide or DPP-4 inhibitors up to August 2016. We extracted data on trial and patient characteristics, and the following outcomes: HbA1c, weight, patients meeting HbA1c <7%, patients experiencing hypoglycemic events, microalbuminuria, estimated glomerular filtration rate (eGFR) and creatinine. We synthesized data using network meta-analyses (NMA) using a Bayesian framework. Continuous outcomes were modeled using normal likelihoods and an identity link, while dichotomous outcomes were modeled using a binomial likelihood and a logit link.</p> <p><b>Results:</b> The systematic literature review yielded 39 publications pertaining to 38 trials. A total of 27 trials (5032 patients) reported change in HbA1c at 12 weeks and at 24 weeks 9 trials (2091 patients). All treatments showed statistically significant reductions in HbA1c relative to placebo at 12 and 24 weeks. Liraglutide 0.9 mg was statistically superior to all DPP-4 interventions (vildagliptin, sitagliptin, linagliptin, alogliptin, teneligliptin, trelagliptin and omarigliptin) at 12 weeks and 24 weeks among those reporting. Treatments were not statistically differentiable with respect to weight change and risk of hypoglycemia. Finally, no comparisons of eGFR and microalbuminuria were conducted, as this data was reported in too few trials to conduct analyses.</p> <p><b>Limitations:</b> Some important outcomes were limited by poor reporting (eGFR and microalbuminuria) or low event rates (hypoglycemia). The follow-up time was relatively short. Clinically, the 24 week time point is more important as it demonstrates more sustained results.</p> <p><b>Conclusions:</b> Our research suggests that liraglutide 0.9 mg offers a more efficacious treatment option for T2DM than the DPP-4 inhibitors among adult Japanese patients and that it is a viable option for this population.</p

Two-Dimensional Microchemical Observation of Mast Cell Biogenic Amine Release as Monitored by a 128 × 128 Array-Type Charge-Coupled Device Ion Image Sensor

Available array-type, chemical-sensing image sensors generally only provide on/off responses to the sensed chemical and produce qualitative information. Therefore, there is a need for an array sensor design that can detect chemical concentration changes to produce quantitative, event-sensitive information. In this study, a 128 × 128 array-type image sensor was modified and applied to imaging of biogenic amines released from stimulated rat mast cells, providing recordable responses of the time course of their release and diffusion. The imaging tool was manufactured by an integrated circuit process, including complementary metal oxide semiconductor and charge-coupled device technology. It was fitted with an amine-sensitive membrane prepared from plasticized poly­(vinyl chloride) including a hydrophobic anion, which allowed the sensor to detect amines, such as histamine and serotonin, in Tyrode’s solution. As mast cells were larger in diameter than the pixel hollows, some pixels monitored amines released from single cells. The image from the array responses yielded sequential snapshots at a practical frame speed that followed amine concentration changes over time, after mast cell amine release was synchronized by chemical stimulation. This sensor was shown to be sensitive to amine release at very low stimulus concentrations and was able to detect localized spots of high amine release. The entire time course of the amine release was recorded, including maximum concentration at 4–6 s and signal disappearance at 30 s after stimulation. With further development, this sensor will increase opportunities to study a variety of biological systems, including neuronal chemical processes

Visual working memory (WM) task.

<p>A: Experimental paradigms of the visual WM task. First, a sample array was presented for 100 ms on the computer display. Each sample array consisted of two, four, or six colored squares at randomized positions (in the present figure, the size of sample array is 6). After a 1,000-ms retention interval, the test stimulus was presented for 2,000ms at one of the sample array positions. Each test cue consisted of two colored rectangles that were half the width of the sample squares. Participates were asked to determine which test stimulus color was the same as the sample square that had been shown at that position. B: Behavioral results from the visual WM task. Data are presented as the group mean of percentage of correct responses, with bars indicating standard errors. The red and blue circles indicate data from AVG experts and non-experts, respectively. The horizontal axis represents sample array size. The percentage of correct responses in AVG experts is significantly greater than in the non-experts in the task with an array size of six. * indicates <i>p</i><0.05 after correction for multiple comparisons (Bonferroni correction).</p

VBM analysis.

<p>A: Group activation superimposed on a standardized anatomical image. Brain region exhibits larger local GM volumes in the right IPL in AVG experts compared with non-experts (FWE-corrected <i>p</i><0.05). The statistical threshold of the displayed image was set to a <i>P</i>-value of 0.001, which was uncorrected for multiple comparisons for display purposes only. B: A scatter-plot portraying the relationship between GM volumes in the right IPL (vertical axis) and the percentage of correct responses (horizontal axis) in the visual WM task with an array size of 6 in AVG experts. The circle represents individual values for AVG experts, and the line indicates the linear fit for these data. A significant positive correlation was observed (<i>p</i><0.05).</p