Efficacy and safety of luseogliflozin added to various oral antidiabetic drugs in Japanese patients with type 2 diabetes mellitus

Introduction: Two studies were carried out to investigate the efficacy and safety of luseogliflozin added to existing oral antidiabetic drugs (OADs) in Japanese type 2 diabetic patients inadequately controlled with OAD monotherapy. Materials and Methods: In the trial involving add‐on to sulfonylureas (study 03‐1), patients were randomly assigned to receive luseogliflozin 2.5 mg or a placebo for a 24‐week double‐blind period, followed by a 28‐week open‐label period. In the open‐label trial involving add‐on to other OADs; that is, biguanides, dipeptidyl peptidase‐4 inhibitors, thiazolidinediones, glinides and α‐glucosidase inhibitors (study 03‐2), patients received luseogliflozin for 52 weeks. Results: In study 03‐1, luseogliflozin significantly decreased glycated hemoglobin at the end of the 24‐week double‐blind period compared with the placebo (–0.88%, P < 0.001), and glycated hemoglobin reduction from baseline at week 52 was –0.63%. In study 03‐2, luseogliflozin added to other OADs significantly decreased glycated hemoglobin from baseline at week 52 (–0.52 to –0.68%, P < 0.001 for all OADs). Bodyweight reduction was observed in all add‐on therapies, even with agents associated with weight gain, such as sulfonylureas and thiazolidinediones. Most adverse events were mild in severity. When added to a sulfonylurea, incidences of hypoglycemia during the double‐blind period were 8.7% and 4.2% for luseogliflozin and placebo, respectively, but no major hypoglycemic episodes occurred. The frequency and incidences of adverse events of special interest for sodium glucose cotransporter 2 inhibitors and adverse events associated with combined OADs were acceptable. Conclusions: Add‐on therapies of luseogliflozin to existing OADs improved glycemic control, reduced bodyweight and were well tolerated in Japanese type 2 diabetic patients. These trials were registered with the Japan Pharmaceutical Information Center (add on to sulfonylurea: JapicCTI‐111507; add on to other OADs: JapicCTI‐111508)

二重房室伝導経路と潜在性WPW症候群を合併した僧帽弁逸脱の1例

聴診および心エコー図上,僧帽弁逸脱を認め頻拍発作を繰り返す37歳男性例に対して電気生理学的検査が行われた.その結果,二重房室伝導経路と潜在性WPW症候群をあわせもつことが判明した.90～220/分の心室ペーシングにて室房(V-A)伝導時間は一定であった.さらにアトロピン投与後120～240/分の心室ペーシングにても室房伝導時間は一定で,逆行性最早期心房興奮部位は左房(室-左房伝導時間は140msec)であった.多部位心房ペーシングにても顕性pre-excitationはみられなかった.これらの所見から左側副伝導路を逆行性に伝導する経路(concealed WPW)の存在が示唆された.本例における発作性上室性頻拍は,slow AV nodal pathwayを順行性に,左側副伝導路を逆行性に伝導する回帰性頻拍と考えられた.僧帽弁逸脱と2種の異常房室伝導路合併との関係は不明であるが,僧帽弁逸脱例に二重房室伝導経路と潜在性WPW症候群を合わせもつことはまれと思われた.An electrophysiologic study was performed on a 37-year-old male with auscultatory and echocardiographic findings of mitral valve prolapsed (MVP), because of frequent episodes of palpitation with tachycardia. It was found to have dual atrioventricular (AV) nodal pathways as well as the concealed Wolff-Parkinson-White (WPW) syndrome. As a result of atrial extrastimulus testing, a discontinuous AV nodal conduction curve, suggesting dual AV nodal pathways, was obtained. The ventriculoatrial (V-A) interval was constant at ventricular paced rates of 90 to 220 beats/min. In addition, ventricular pacing at a rate of 120 to 240/min after atropine revealed a V-A conduction time identical to that in the control period, and the earliest retrograde atrial activation occurred on left atrial site (LA) with a V-LA interval of 140 msec. Manifest pre-excitation was not demonstrated by means of pacing at multiple atrial sites. These findings suggested the presence of retrograde conduction via only the left-sided accessory pathway (concealed WPW syndrome). In this patient, paroxysmal supraventricular tachycardia was re-entrant arrhythmia utilizing the slow AV nodal pathway for antegrade conduction and the left-sided accessory pathway for retrograde conduction. Although the relationships of MVP and the combination of these two abnormal AV conduction pathways are unknown, this appears to be a rare case of coexistence of the dual AV nodal pathways and the concealed WPW syndrome in a patient with MVP

ステロイド投与により肺高血圧が著明に改善した進行性全身性硬化症の1例 : 原発性胆汁性肝硬変症の合併例

著明な肺高血圧による右心不全症状を呈した進行性全身性硬化症の1例を報告する.本例は,ステロイドが皮膚病変に対して有効でなかった時期にもかかわらず,肺高血圧には著効を示し,原発性胆汁性肝硬変症の合併を認めるまれな症例と考えられた.A patient with progressive systemic sclerosis and right ventricular failure secondary to pulmonary hypertension was reported. Although steroid therapy was ineffective for her skin lesion, it was remarkably effective for her pulmonary hypertension. She also had a rare complication of primary biliary cirrhosis

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension