Therapeutic Research

症例は60 歳，男性。2014 年1 月に左房粘液腫切除術施行。右側左房と右心房切開でアプローチし心房中隔の腫瘍を切除した。2014 年4 月にマクロリエントリー性心房頻拍（AT）に対しアブレーションを施行した。右房分界稜上部の緩徐伝導部位への通電にて頻拍は停止し，さらに三尖弁下大静脈峡部（CTI）にブロックラインを追加作成し手技終了した。2017年5月にATが再発し，同年8月に再セッションを行った。Mini –basketカテーテルを用いて高密度右房マップを作成した。CTIに2 ヵ所の伝導間隙を確認，追加通電にてCTI両方向性ブロックを再完成させた。右房頻回刺激にてAT–1（周期長: 256 ms）が誘発，高密度マップにて分界稜下部を緩徐伝導するATと診断し，同部位への追加通電を行い頻拍は停止した。再度の右房頻回刺激にてAT –2（225 sm）が誘発された。同頻拍は右房側壁の切開線周囲を旋回するATであり，切開線下部から下大静脈にかけて伝導間隙を確認，同部位の通電にて頻拍は停止した。以後いかなる頻拍も誘発されず，さらに分界稜下部を横断する伝導ブロックも確認し手技終了した。粘液腫切除後に複数のマクロリエントリー性心房頻拍を認め，Rhythmiaシステムにより短時間で正確な頻拍回路の同定，さらに必須緩徐伝導路のブロックライン作成を確認しえた症例を経験したので報告する。

Objectives：We evaluated the effectiveness of a dipeptidyl peptidase‒4 inhibitor （DPP‒4i）as add‒on therapy to metformin and of dose‒escalation of metformin in Japanese patients with type 2 diabetes mellitus（T2DM）prescribed metformin （500 mg/day） using a real‒world clinical database. Methods：Data of T2DM patients were extracted from the health insurance administrative claims database of Medical Data Vision Company based on continued treatment with metformin 500 mg/day for ≧3 months. The first analysis cohort was“DPP‒4i add‒on”that was composed of the patients who initiated a DPP‒4i as add‒on therapy to metformin for ≧12 month. The second cohort was“metformin dose escalation”that was composed of patients treated with escalated dose of metformin（＞500 mg/day）after ≧12 month without a DPP‒4i. The changes of HbA1c levels from baseline were assessed over 12 months in the cohorts. Results：For the DPP‒4i add‒on cohort（n＝689）, the changes in HbA1c levels, mean±SD（n）, at 3, 6 and 12 months and over the evaluation period were －0.3 ±0.8％ （650）, －0.3±0.8％（621）, －0.2±0.9％（577）and －0.2±0.9％（689）, respectively, and for the metformin dose‒escalation cohort（n＝1194）, －0.2 ±0.9％（1124）, －0.3± 0.9％（1081）, －0.3±0.9％（1008）and －0.3±0.9％（1194）, respectively. All the changes were statistically significant（p＜0.0001）. Subgroup analysis of the metformin dose‒escalation cohort revealed that 1000 mg/day, but not 750 mg/day, of metformin monotherapy was effective. Conclusions：These results indicate that the DPP‒4i add‒on and metformin dose‒escalation（1000 mg/day）in Japanese T2DM patients were effective in controlling blood glucose levels in real‒world clinical practice settings.

The effects of empagliflozin were evaluated on seasonal increase of body weight and HbA1c in Japanese type 2 diabetic（T2DM）patients. In 19 patients with T2DM, both body weight and HbA1c were significantly increased from November 2015 to next February 2016 before the start of empagliflozin. At next season after the start of oral administration of 10 mg/day empagliflozin, no increase of body weight and HbA1c were found at all. Seasonal increase of HbA1c from Novermber to next February was significantly reduced by empagliflozin. It suggests that empagliflozin attenuated seasonal worsening of glycaemic control in Japanese T2DM patients.

Some combination of drugs under one‒dose packaging has been reported to cause changes in tablet appearance and/or dissolution behavior. In this study, changes in appearance and dissolution behavior of Bayaspirin(R) tablet and different telmisartan preparations（a brand‒name drug, Micardis(R), and 11 generic drugs）were examined after one‒week contact with or without one‒dose packaging. Bayaspirin(R) 100 mg tablet and each telmisartan 40 mg tablet were stored at 30℃ with 75％RH for one week, being placed in a 48‒well plate with the surfaces of the two tablets in contact or under one‒dose packaging. Change in appearance was evaluated by visual inspection, and if any change was observed, dissolution behavior and residual rate of Bayaspirin(R) tablet and each telmisartan tablet were assessed. Color changes in the tablet appearance were observed for the combinations of Bayaspirin(R) tablet contacted with 3 telmisartan tablets（Micardis®, telmisartan“DSEP” or telmisartan“YD”tablets）. As for the dissolution test of Bayaspirin(R) tablet contacted with Micardis(R) tablet or telmisartan“DSEP”tablet without one‒packaging, drug dissolution in the 1st fluid for dissolution test（pH 1.2）and rapid resolution in the 2nd fluid for dissolution test（pH 6.8）were observed. Same alternations of the dissolution behavior were observed for the Bayaspirin(R) tablet contacted with Micardis(R) tablet（8 out of 12 samples）or telmisartan“DSEP”tablet（9 out of 12 samples）after one week one‒dose packaging. Dissolution of telmisartan OD“TOWA”was delayed with or without contact with Bayaspirin(R) tablet. No change was observed in the residual rate of aspirin or telmisartan formulations in any preparation. Based on the findings, storage of Bayaspirin(R) tablet in a direct contact with Micardis(R) tablet or telmisartan“DSEP”tablet is not recommended neither with or without one‒dose packaging, since the aspirin tablet with altered dissolution behavior may cause gastric mucosal injury in patients who take those.

SGLT2阻害薬エンパグリフロジン10 mgの併用が著効した，肥満のある陳旧性心筋梗塞を合併した2 型糖尿病の男性症例を経験したので報告する。本例において，エンパグリフロジン投与前6 日間と投与後9 日間の血糖値の変動をFree-Style リブレPro を用いて測定した。さらに，食事内容（カーボ比）の記録と対比して検討した結果，毎食の摂取糖質量は投与の前後でほぼ同じであったが，投与開始後には高血糖のピークを十分に抑えることができた。また，投与前後の血糖の日内変動パターンでも著明な改善が認められた。すなわち，投与開始前後の調査期間内での推定HbA1c は，それぞれ6.7％と5.9％（－0.8％），平均血糖値は147 mg/dL と122 mg/dL（－25 mg/dL），血糖値が目標範囲内であった時間は54％と74％（＋20％）であった。なお，HbA1c の実測値は，短期間にもかかわらず，投与前8.1％から投与後7.5％に低下した。一方，本症例が過去にSGLT2阻害薬を服用していた際の体重，体脂肪量，筋肉量のデータでは，運動を積極的に行っていた時期には体脂肪の減少による理想的な体重減少が得られているが，運動の中断により筋肉量の減少が体重減少の主体になることが示され，SGLT2 阻害薬を投与する際の運動療法の必要性が再認識された。