Relationship between the dose titration and adherence of mirogabalin in patients with peripheral neuropathic pain depending on renal function: a nationwide electronic medical record database study

[Background] Mirogabalin has been attracting attention for treating peripheral neuropathic pain. The package insert recommends that mirogabalin should be titrated depending on renal function. Here, we investigated the relationship between dose titration patterns and adherence, and persistence of mirogabalin treatment. [Research design and methods] Peripheral neuropathic pain patients who initiated mirogabalin between March 2020 and May 2021 were identified using an electronic medical record database. The dose titration pattern was described according to degrees of renal function. Regression analyses were performed to compare adherence and persistence between the patients with and without titration. [Results] Of the 4, 138 identified patients, 1, 696 (41.0%) titrated the dose within 45 days and were more adherent than those without titration (Adjusted odds ratio: 1.75, 95% CI 1.21, 2.54). Of the total 952 patients with renal function parameters, 229 (24.1%) titrated to the effective dose within 45 days and were less likely to discontinue than those without titration (Adjusted hazard ratio: 0.57, 95% CI 0.40, 0.81). [Conclusion] Mirogabalin dose titration was associated with better adherence and persistence. It is important for mirogabalin treatment to determine the initial prescription dose based on renal function and subsequent dose titration according to the package insert. [Trial registration] UMIN00004731

Study of Sustained Blood Pressure-Lowering Effect of Azelnidipine Guided by Self-Measured Morning and Evening Home Blood Pressure: Subgroup Analysis of the At-HOME Study

BACKGROUND: Morning hypertension is a risk factor for cardiovascular and cerebrovascular events, and consequently diagnosis and control of morning hypertension are considered very important. We previously reported the results of the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) Study, which indicated that azelnidipine effectively controlled morning hypertension. OBJECTIVES: The objective of this At-HOME subgroup analysis was to evaluate the sustained blood pressure (BP)-lowering effect of azelnidipine, using mean morning and evening systolic BP [ME average] and morning systolic BP minus evening systolic BP (ME difference). METHODS: We analyzed the self-measured home BP data (measured in the morning and at bedtime) from this 16-week prospective observational study to clarify the effect of morning dosing of azelnidipine (mean [± standard deviation] maximum dose 14.3 ± 3.6 mg/day). A subgroup of patients from the At-HOME Study who had an evening home BP measurement within 28 days prior to the baseline date were used for efficacy analysis (n = 2,546; mean age, 65.1 years; female, 53.6 %). RESULTS: Home systolic BP/diastolic BP levels in the morning and evening were significantly lowered (p < 0.0001) by −19.4 ± 17.1/−10.3 ± 10.6 and −16.9 ± 17.0/−9.4 ± 10.6 mmHg, respectively. Home pulse rates in the morning and evening were also significantly lowered (p < 0.0001) by −3.5 ± 7.8 and −3.5 ± 7.3 beats/min, respectively. At baseline, patients whose ME average was ≥135 mmHg and whose ME difference was ≥15 mmHg (defined as morning-predominant hypertension) accounted for 20.4 % of the study population. However, at the end of the study, the number of such patients was significantly reduced to 7.9 % (p < 0.0001). Patients whose ME average was ≥135 mmHg and whose ME difference was <15 mmHg (defined as sustained hypertension) accounted for 71.1 % of the study population at baseline. This was reduced significantly to 42.8 % at the end of the study (p < 0.0001). ME average decreased significantly from 153.8 ± 15.5 mmHg to 135.6 ± 11.9 mmHg, and ME difference also decreased significantly from 6.7 ± 13.1 mmHg to 4.7 ± 10.8 mmHg (both p < 0.0001). CONCLUSION: These results suggest that azelnidipine improved morning hypertension with its sustained BP-lowering effect. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-013-0007-7) contains supplementary material, which is available to authorized users

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study

Introduction Clinical data of esaxerenone in hypertensive patients with diabetic kidney disease (DKD) are lacking. We evaluated the efficacy and safety of esaxerenone in patients with DKD and an inadequate response to blood pressure (BP)-lowering treatment. Methods In this multicenter, open-label, prospective study, patients were divided into urinary albumin-to-creatinine ratio subcohorts (UACR  Results In total, 113 patients were enrolled. Morning home SBP/DBP significantly decreased from baseline to EOT in the total population (− 11.6/− 5.2 mmHg, both p  Conclusion Esaxerenone demonstrated a BP-lowering effect and improved albuminuria. The effects were consistent regardless of the severity of albuminuria without clinically relevant serum potassium elevation and eGFR reduction

Quantitative Evaluation of Compliance with Recommendation for Sulfonylurea Dose Co-Administered with DPP-4 Inhibitors in Japan

After the launch of dipeptidyl peptidase-4 (DPP-4), a new oral hypoglycemic drug (OHD), in December 2009, severe hypoglycemia cases were reported in Japan. Although the definite cause was unknown, co-administration with sulfonylureas (SU) was suspected as one of the potential risk factors. The Japan Association for Diabetes Education and Care (JADEC) released a recommendation in April 2010 to lower the dose of three major SUs (glimepiride, glibenclamide, and gliclazide) when adding a DPP-4 inhibitor. To evaluate the effectiveness of this risk minimization action along with labeling changes, dispensing records for 114,263 patients prescribed OHDs between December 2008 and December 2010 were identified in the Nihon-Chouzai pharmacy claims database. The adherence to the recommended dosing of SU co-prescribed with DPP-4 inhibitors increased from 46.3% before to 63.8% after the JADEC recommendation (p &lt; 0.01 by time-series analysis), while no change was found in those for SU monotherapy and SU with other OHD co-prescriptions. The adherence was significantly worse for those receiving a glibenclamide prescription. The JADEC recommendation, along with labeling changes, appeared to have a favorable effect on the risk minimization action in Japan. In these instances, a pharmacy claims database can be a useful tool to evaluate risk minimization actions

G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients

Abstract Aims/Introduction Pancreatic β‐cell dysfunction contributes to type 2 diabetes mellitus progression. Drugs that improve insulin secretion might be a valuable treatment approach. The present study aimed to evaluate the effect of the G protein‐coupled receptor 119 agonist DS‐8500a on insulin secretory capacity in Japanese type 2 diabetes mellitus patients. Materials and Methods This single‐center, 4‐week, randomized, double‐blind, cross‐over study enrolled 21 Japanese drug‐naïve type 2 diabetes mellitus patients aged ≥20 years with glycated hemoglobin ≥7.0 and <9.0% (NCT02669732, JapicCTI 163126). Patients received 75 mg of DS‐8500a or a placebo orally daily for 4 weeks in a random order. A combined euglycemic‐hyperinsulinemic and hyperglycemic clamp test was carried out to assess insulin secretion and insulin sensitivity before and after each 4‐week treatment period. Primary end‐points were first‐phase insulin secretion (insulin area under the curve [AUC]180–190 min and C‐peptide AUC180–190 min during the clamp test) and second‐phase insulin secretion (insulin AUC190–300 min and C‐peptide AUC190–300 min). Insulin sensitivity (M and M/I values), disposition index and changes in lipid profile were also assessed. Results DS‐8500a significantly increased first‐ and second‐phase insulin AUC (P = 0.0011, P = 0.0112) and C‐peptide AUC (P = 0.0012, P < 0.0001) compared with the placebo. At day 28, M and M/I values were comparable with those of the placebo, whereas the disposition index for insulin and C‐peptide was significantly increased (P = 0.0108, P = 0.0002). Total cholesterol, low‐density lipoprotein cholesterol and triglyceride concentrations were significantly reduced, and high‐density lipoprotein cholesterol concentrations were significantly increased compared with the placebo. No significant treatment‐emergent adverse events occurred. Conclusion DS‐8500a enhanced insulin secretory capacity, but not insulin sensitivity

A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME) Study

Background: Morning blood pressure (BP) surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS)-restoring Ca-channel blocker (CCB) azelnidipine (AZ) on this age-related morning BP increase. Methods: We conducted a 16-week prospective study to clarify the effect of morning dosing of AZ on home BPs measured in the morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years; female, 53.6%). Results: At baseline, ME-Dif (morning systolic BP [SBP]–evening SBP) increased with age, independently of ME-Ave (average of the morning and evening SBPs). This age-related increase of ME-Dif was exaggerated by regular alcohol drinking and beta-blocker use. After AZ treatment (14.3 ± 3.6 mg/day), ME-AV and ME-Dif were significantly reduced independently of each other, with reductions of –18.1 ± 15.6 and –2.5 ± 13.2 mmHg, respectively (both p &lt; 0.001). AZ treatment decreased age-related increase in ME-Dif particularly in patients who were regular consumers of alcohol and in beta-blocker users. Conclusions: The new BRS-restoring CCB AZ significantly reduced age-related increase in morning BP and had some potential benefit on cardiovascular protection in hypertension, particularly in elderly patients and/or consumers of alcohol

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

Pharmacokinetics and Safety of DS-8500a, an Anti-diabetic Drug, in Japanese Subjects with Hepatic or Renal Impairment: A Single-center, Open-label, Single-dose Study

<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><a href="https://link.springer.com/article/10.1007/s12325-018-0739-4">https://link.springer.com/article/10.1007/s12325-018-0739-4</a></p><p></p><p></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>• Audio slides</p><br><p></p