國(guó)人服用Amaryl單日一次與單日二次劑量之糖化血色素評(píng)估

1、國(guó)人服用Amaryl單日一次與單日二次劑量之糖化血色素評(píng)估Evaluation HbA1c of once- versus twice-daily administration of glimepiride in Taiwan patients with non-insulin-dependent diabetes mellitus研究動(dòng)機(jī)研究動(dòng)機(jī)t國(guó)外有相關(guān)報(bào)導(dǎo)t國(guó)內(nèi)醫(yī)師使用S-U習(xí)慣未完全改變t病人使用QD降血糖藥物沒信心t國(guó)內(nèi)醫(yī)師臨床經(jīng)驗(yàn)BID使用效果略好tQD or BID 於國(guó)人是否有顯著差異?t評(píng)估糖化血色素及副作用?國(guó)外研究tShort-term comparison of on

2、ce- versus twice-daily administration of glimepiride in patients with non-insulin-dependent diabetes mellitust15-week study involved 161 subjects with NIDDMtRandomized into two groupstFor 4 weeks, group 1 received 3 mg twice dailytGroup 2 received glimepiride 6 mg once dailytAfter a 3-week placebo-w

3、ashout period；were crossed over tConcentration recorded at 20 time points over a 24-hourtInsulin and C-peptide concentrations were recorded at 16 time國(guó)外研究結(jié)果t94 completed the entire studytEqually effective in reducing concentrations of fasting, postbreakfast, postlunch, and postdinner plasma glucoset

4、Glucose conc. showed a slightly greater decrease from baseline for the twice-daily regimentDifference between the regimens was statistically significant but not clinically meaningfultHeadache, in more than 5% of the subjects國(guó)外研究結(jié)論tEqually effective :once or twice dailytSeems to stimulate insulin pro

5、duction primarily after meals,when plasma glucose conc. are highesttControls blood glucose throughout the dayAmaryl單日一次與單日二次劑量之糖化血色素評(píng)估 - 可行性評(píng)估可行性評(píng)估t單獨(dú)服用Amaryl病人不少t以病歷即可得知病人HbA1c數(shù)值t仍有醫(yī)師告知病人BID服用t可找醫(yī)師配合t以醫(yī)療系統(tǒng)即可查詢使用Amaryl之病人t除門診外，可從住院病人開始著手糖化血色素評(píng)估條件tNIDDM, 最好選擇單獨(dú)使用Amaryl之病人t無(wú)服用交互作用藥物 a. Thiazides and o

6、ther diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, High-protein binding, aspirin, warfarin, and isoniazid,( lipitor) b. P450 II C9 also include phenytoin, diclofenac, ibuprofen, naproxen, and mefenamic acidt

7、同時(shí)服用Amaryl+ACEI, Inderal, Ca-blocker無(wú)臨床上差異糖化血色素評(píng)估條件t不可選擇同時(shí)服用兩種以上將血糖藥t無(wú)嚴(yán)重之肝功能障礙t劑量設(shè)定 a. 2mg QD; 1mg BID b.4mg QD; 2mg BIDt已經(jīng)使用Amaryl一個(gè)月以上之病人(慢籤) 病情穩(wěn)定(無(wú)調(diào)整劑量)、有定期回診t徵求詢問願(yuàn)意配合之病人同意病人需配合之條件t每週最少監(jiān)測(cè)三次飯前血糖t每週量一次體重t每個(gè)月測(cè)量一次HbA1ct確實(shí)填寫副作用紀(jì)錄表t按時(shí)服藥決定臨床試驗(yàn)設(shè)計(jì)tTwo Group Pair design 同一樣品使用於不同之治療組 Parallel Design不同一樣品使用

8、於不同之治療組t國(guó)人服用Amaryl單日一次與單日二次劑量之糖化血色素評(píng)估Two sample(兩組QD,BID); 比例性; Pair design Paired Students T-test Sample Sizet兩組成對(duì)母群體之樣品數(shù)預(yù)估 預(yù)估使用qd HbA1c 7.9%, BidHbA1c 7.4%t預(yù)估SD為0.4%, =0.05,0.01; =0.2,0.1tN=(/)2 (Z+Z)2+0.5Z2 N=(0.4/0.5) 2 (1.96+0.84) 2+0.5(1.96)2=6.9384 N=(0.4/0.5) 2 (2.576+1.282) 2+0.5(2.576)2=12

9、.84糖化血色素評(píng)估方法（一）t評(píng)估人數(shù)18-30人，共18週(4.5月)t前八週Group A- 4mg QD 4 mg QD 後八週 Group B-2mg BID 2mg BID Cross over and 2 weeks ( t1/2約58小時(shí))t同時(shí)發(fā)予副作用統(tǒng)計(jì)問卷t統(tǒng)計(jì)HbA1c 、AC sugar方便且較有意義t困難: 醫(yī)師要協(xié)助告知病患何時(shí)改變頻次糖化血色素評(píng)估方法（二）t評(píng)估人數(shù)60以上人，共約4-6月t病例回顧曾經(jīng)使用Amaryl BID之病人，現(xiàn)今已QD使用之病人t副作用統(tǒng)計(jì)問卷電話追蹤訪問t比較不同組別HbA1c，AC sugartSample size要夠多，難以

10、控制過去用藥情況t統(tǒng)計(jì)方法難且較少臨床意義t不須醫(yī)師配合副作用統(tǒng)計(jì)評(píng)估（一） 副作用統(tǒng)計(jì)表 月份副作用 次五月六月七月八月12329.3012329.3012329.3012329.30頭昏眼花 -無(wú)力-噁心腹瀉 -頭痛皮膚搔癢 -紅斑低血糖 正HbA1c統(tǒng)計(jì)t 檢定：兩個(gè)母體平均數(shù)差的檢定，假設(shè)變異數(shù)相等QDBID平均數(shù)7.7666677.655555556變異數(shù)0.06250.082777778觀察值個(gè)數(shù)99Pooled 變異數(shù)0.072639假設(shè)的均數(shù)差0自由度16t 統(tǒng)計(jì)0.874539P(T=t) 單尾0.197381臨界值：?jiǎn)挝?.745884P(T=t) 雙尾0.394763臨界值