Study Protocol for the Initial Choice of DPP-4 Inhibitor in Japanese Patients with Type 2 diabetes Mellitus: Effect of Linagliptin on QOL (INTEL-QOL) Trial

<p></p><p><b>Article full text</b></p><p><br></p><p>The full text of this article can be found here<b>. </b><u>https://link.springer.com/article/10.1007/s13300-018-0437-x</u></p><p><u><br></u></p><p><b>Provide enhanced content for this article</b></p><p><br></p><p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p><p><br></p><p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p><p><br></p><p>Other enhanced features include, but are not limited to:</p><p><br></p><p>• Slide decks</p><p>• Videos and animations</p><p>• Audio abstracts</p><p> </p><p>• Audio slides</p><p></p

Efficacy and Safety of GPR119 Agonist DS-8500a in Japanese Patients with Type 2 Diabetes: a Randomized, Double-Blind, Placebo-Controlled, 12-Week Study

<p><b>Article full text</b></p><p><br></p><p>The full text of this article can be found here<b>.</b> <a href="https://link.springer.com/article/10.1007/s12325-018-0668-2">https://link.springer.com/article/10.1007/s12325-018-0668-2</a></p><p></p><p><br></p><p><b>Provide enhanced content for this article</b></p><p><br></p><p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p><p><br></p><p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p><p><br></p><p>Other enhanced features include, but are not limited to:</p><p><br></p><p>• Slide decks</p><p>• Videos and animations</p><p>• Audio abstracts</p><p> </p><p>• Audio slides</p><ul> </ul> <p> </p> <p> </p

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

<p><b>Article full text</b><br></p> <p><br></p> <p>The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-017-0351-7"><b>here</b>.</a></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p> </p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p> <p> </p> <p> </p

SAT-139 Clinical Impact of Oral Semaglutide Compared with Sitagliptin in T2D on Metformin ± Sulfonylurea: The Pioneer 3 Trial.

Long-term effects, safety and tolerability of oral semaglutide (SEMA; a GLP-1 receptor agonist [GLP-1RA]) vs sitagliptin (SITA) as add-on to metformin ± sulfonylurea was investigated in patients (pts) with T2D in a 78-week, double-blind, double-dummy trial. Pts were randomized to once daily oral SEMA 3 mg (N=466), 7 mg (N=466) or 14 mg (N=465), or SITA 100 mg (N=467). Primary endpoint was change in HbA, confirmatory secondary endpoint was change in body weight, both from baseline to week 26. Two estimands were defined (‘treatment policy [TPol] estimand’: treatment effect regardless of trial product discontinuation and rescue medication use; ‘trial product estimand’: treatment effect assuming on trial product without rescue medication use) in all randomized pts. Confirmatory testing was based on the TPol estimand; within each dose level, non-inferiority for the primary endpoint (non-inferiority margin: 0.3%) had to be confirmed before testing superiority for the primary and confirmatory secondary endpoints. Estimated week 26 HbA reductions with 7 and 14 mg were –1.0% and –1.3%, vs –0.8% with SITA, and were superior (TPol estimand; estimated treatment difference vs SITA [ETD; 95% CI]: –0.3% [–0.4, –0.1]; –0.5% [–0.6, –0.4]; both P<0.001). Non-inferiority of 3 mg vs SITA was not confirmed (ETD: 0.2% [0.1, 0.3]; P=0.09); HbA reductions favored SITA (P=0.008). Similar results were obtained with the trial product estimand at week 26 (ETD: –0.3% [–0.4, –0.2]; –0.6% [–0.7, –0.5] for 7 and 14 mg; both P<0.001 favoring oral SEMA; 0.2% [0.1, 0.4] for 3 mg; P<0.001 favoring SITA). At week 78, HbA reductions with 14 mg were statistically significantly greater vs SITA for both estimands; there was no statistically significant difference with 3 mg (both estimands) or 7 mg (TPol estimand). All oral SEMA doses significantly lowered body weight vs SITA at week 26 for the TPol estimand (ETD: –0.6 kg [–1.1, –0.1]; –1.6 kg [–2.0, –1.1]; –2.5 kg [–3.0, –2.0] for 3, 7 and 14 mg; all P<0.02), confirming superiority of 7 and 14 mg (3 mg superiority not tested), and the trial product estimand (ETD: –0.5 kg [–1.0, –0.1]; –1.5 kg [–2.0, –1.1]; –2.6 kg [–3.1, –2.1] for 3, 7 and 14 mg; all P<0.03). Week 78 body weight reductions were also statistically significant, favoring oral SEMA (all doses, both estimands). Adverse events (AEs) occurred similarly across treatment arms. The most common AE with oral SEMA was transient mild/moderate nausea, affecting 7.5–15.7% of pts. Serious AEs were reported by 13.7%, 10.1% and 9.5% of pts for 3, 7 and 14 mg, and 12.4% for SITA. AEs led to premature trial product discontinuation in 5.6%, 5.8% and 11.6% of pts for 3, 7 and 14 mg, and 5.2% for SITA, mainly due to gastrointestinal AEs. In conclusion, oral semaglutide 7 and 14 mg provided statistically superior HbA and body weight reductions at week 26 compared with SITA 100 mg (TPol estimand). Safety and tolerability were consistent with other GLP-1RAs.</div

The Influence of Sitagliptin on Treatment-Related Quality of Life in Patients with Type 2 Diabetes Mellitus Receiving Insulin Treatment: A Prespecified Sub-Analysis

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-017-0267-2"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p

Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies

<div><p>Aim</p><p>We performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and six susceptibility loci (<i>TMEM154</i>, <i>SSR1</i>, <i>FAF1</i>, <i>POU5F1</i>, <i>ARL15</i>, and <i>MPHOSPH9</i>) originally identified by a transethnic meta-analysis of genome-wide association studies (GWAS) in 2014.</p><p>Methods</p><p>We genotyped 7,620 Japanese participants (5,817 type 2 diabetes patients and 1,803 controls) for each of the single nucleotide polymorphisms (SNPs) using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using logistic regression analysis.</p><p>Results</p><p>Of the six SNPs examined in this study, four (rs6813195 near <i>TMEM154</i>, rs17106184 in <i>FAF1</i>, rs3130501 in <i>POU5F1</i> and rs4275659 near <i>MPHOSPH9</i>) had the same direction of effect as in the original reports, but two (rs9505118 in <i>SSR1</i> and rs702634 in <i>ARL15</i>) had the opposite direction of effect. Among these loci, rs3130501 and rs4275659 were nominally associated with type 2 diabetes (rs3130501; p = 0.017, odds ratio [OR] = 1.113, 95% confidence interval [CI] 1.019–1.215, rs4275659; p = 0.012, OR = 1.127, 95% CI 1.026–1.238, adjusted for sex, age and body mass index), but we did not observe a significant association with type 2 diabetes for any of the six evaluated SNP loci in our Japanese population.</p><p>Conclusions</p><p>Our results indicate that effects of the six SNP loci identified in the transethnic GWAS meta-analysis are not major among the Japanese, although SNPs in <i>POU5F1</i> and <i>MPHOSPH9</i> loci may have some effect on susceptibility to type 2 diabetes in this population.</p></div

Correlations between myocardial TG content and MRI parameters.

<p>A: A correlation between myocardial TG content and end-diastolic volume. B: A correlation between myocardial TG content and end-systolic volume. C: Correlation between myocardial TG content and left ventricular (LV) mass. D: Correlation between myocardial TG content and epicardial fat volume. Open circle; control group. Closed circle; athlete group.</p

Comparison between myocardial TG content in the control group and the athlete group.

<p>* <i>P</i><0.05 between the two groups.</p

Replication Study for the Association of 9 East Asian GWAS-Derived Loci with Susceptibility to Type 2 Diabetes in a Japanese Population

<div><p>Aims</p><p>East Asian genome-wide association studies (GWAS) for type 2 diabetes identified 8 loci with genome-wide significance, and 2 loci with a borderline association. However, the associations of these loci except <i>MAEA</i> locus with type 2 diabetes have not been evaluated in independent East Asian cohorts. We performed a replication study to investigate the association of these susceptibility loci with type 2 diabetes in an independent Japanese population.</p> <p>Methods</p><p>We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and 2,064 controls) for each of the 9 single nucleotide polymorphisms (SNPs), rs7041847 in <i>GLIS3</i>, rs6017317 in <i>FITM2</i>−<i>R3HDML</i>−<i>HNF4A</i>, rs6467136 near <i>GCCI</i>−<i>PAX4</i>, rs831571 near <i>PSMD6</i>, rs9470794 in <i>ZFAND3</i>, rs3786897 in <i>PEPD</i>, rs1535500 in <i>KCNK16</i>, rs16955379 in <i>CMIP</i>, and rs17797882 near <i>WWOX</i>. Because the sample size in this study was not sufficient to replicate single SNP associations, we constructed a genetic risk score (GRS) by summing a number of risk alleles of the 9 SNPs, and examined the association of the GRS with type 2 diabetes using logistic regression analysis.</p> <p>Results</p><p>With the exception of rs1535500 in <i>KCNK16</i>, all SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. The GRS constructed from the 9 SNPs was significantly associated with type 2 diabetes in the Japanese population (<i>p</i> = 4.0 × 10^-4, OR = 1.05, 95% confidence interval: 1.02–1.09). In quantitative trait analyses, rs16955379 in <i>CMIP</i> was nominally associated with a decreased homeostasis model assessment of β-cell function and with increased fasting plasma glucose, but neither the individual SNPs nor the GRS showed a significant association with the glycemic traits.</p> <p>Conclusions</p><p>These results indicate that 9 loci that were identified in the East Asian GWAS meta-analysis have a significant effect on the susceptibility to type 2 diabetes in the Japanese population.</p> </div

Representative results of H¹-MR spectra in a healthy subject.

<p>A: Myocardial voxel localization for H¹-MRS in 4-chamber and short axis views. B: H¹-MR spectra without water suppression. C: H¹-MR spectra without water suppression.</p