This is to introduce the evolution of Hyperlipidemia Guideline in the US and Taiwan. SInce low dose Crestor threapy is common in Taiwan, we survey the efficacy of Crestor therapy at the dose lower than 5mg per day. Meanwhile, we compare the effect of daily and alternative day dosing of Crestor.
This is to introduce the evolution of Hyperlipidemia Guideline in the US and Taiwan. SInce low dose Crestor threapy is common in Taiwan, we survey the efficacy of Crestor therapy at the dose lower than 5mg per day. Meanwhile, we compare the effect of daily and alternative day dosing of Crestor.
2. The total number of patients of Diabetes mellitus was 1,110,941 (547,051 males and 563,890 females), accounting for 4.90% more of the total population (DOH) 02/01/12
19. Glufast ® 僅 < 25% 經 CYP 代謝途徑 ， 藥物交互作用少 。 極少有活性代謝物，可適用於腎功能不全患者 CO 2 H N H H H O UGT1A3 UGT1A9 葡萄糖醛酸 化作用 (glucuronidation) 約 74 ％ Mitiglinide CYP 2C9 氧化 ＜ 25 ％ Hydroxy - 5α-Hydroxy - 5β-Hydroxy - 4α-Hydroxy - 4β-Hydroxy - 3aβ-Hydroxy - O Gluc . N H H H O O 葡萄糖醛酸結合 體
20. Glufast ® 可快速刺激 early-phase 胰島素分泌 Mechanism of G lufast Glufast SU SU receptor Pancreas Insulin Blood Insulin level Administration Glufast SU Insulin Pancreatic beta cell SU receptor Time Pancreatic beta cell
23. Mitiglinide has 1000 fold higher affinity to SUR1 (IC 50 =4 nM), than to SUR2A (IC 50 =3 μ M) and SUR2B ( IC 50 =5 μ M) Beta Cell Cardiomyocyte Smooth Muscle Cell Reimann F, et al. Bri J Pharmacol 2001;132:1542-1548 Mitiglinide inhibits Kir6.2/SUR currents at two site: A low affinity site on Kir6.2, a high affinity site on SUR
24. G lufast ® is safe to heart Glufast SUR2A SUR1 Pancreatic beta cell Pancreas Heart Glufast selectively binds to SU receptor (SUR1) in pancreas beta cells. Glufast dose not bind to SU receptor (SUR2A) in heart . Glufast acts pancreas beta cells only, not act on heart. Reimann, F. et al .: Britsh Journal of Pharmacology, 132: 1542, 2001. Pancreatic β cell Expression organ Mitiglinide IC 50 （ mol/L ） K ATP channel Cardiac muscle Smooth muscle 3.8×10 -9 3.2×10 -6 4.6×10 -6 SUR1/Kir6.2 SUR2A/Kir6.2 SUR2B/Kir6.2
26. 低血糖症狀發生率 與 Placebo 相似 組 對象 病例數 發現 病例數 發生率 (%) p=0.650 χ 2 檢定 Placebo 2.9 3 102 Glufast 10mg 102 2 2.0 Data on Japan Kissei file
27. Glufast ® 適合於年長 ( ＞ 60 歲 ) 及初始病友 (A1C ＜ 8%) The Journal International Medical Research 2009; 37:812-821
28. A Randomized, Double-blind, Placebo-control, Metformin Add-on Study to Evaluate the Efficacy and Safety of Mitiglinide in Patients with Type 2 Diabetes Mellitus 九醫學中心 : 台大、北榮、長庚、三總、新光、馬偕、慈 濟、中國、彰基 Taiwan Glufast ® clinical study
33. AEs occurred during treatment period Note: N= the number of patients in the analysis population. n= the number of patients with the event. (%)= n/N*100. -A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment. *p-value from the comparsion of event incidence between treatment group by using Fisher's exact test Variable Glufast N= 73 n(%) Placebo N= 72 n(%) P-value* - AE number 105 88 - AE incidence rate 42 (57.53%) 36 (50.00%) 0.4069 - Maximum Severity: Mild 31 ( 42.47) 23 ( 31.94) 0.2300 Moderate 8 ( 10.96) 11 ( 15.28) 0.4710 Severe 3 ( 4.11) 2 ( 2.78) 1.0000 - Drug-related AE incidence rate 10 ( 13.70) 6 ( 8.33) 0.4276 Diarrhea 3 ( 4.11) 3 ( 4.17) 1.0000 Increased Appetite 3 ( 4.11) 0 ( 0.00) 0.2448 Sweating 3 ( 4.11) 0 ( 0.00) 0.2448
44. Mitiglinide decreases the postprandial generation of oxidative stress and inflammation in type 2 diabetic patients Assaloni R, et al. Diabetologia 2005;48:1919-1924
48. Glinide 比較 Brand name Novonorm (1mg) Starlix (120mg) Glufast (10mg) Product name Repaglinide Nateglinide Mitiglinide Recommended dose 0.5-4 mg tid; max.:16mg 60-180 mg tid 10-20 mg tid Administration time Before meal, 15-30 min Before meal, 1-30 min Before meal, 隨餐服用 T max 0.5-1 hr 0.25-1 hr 14 mins T 1/2 1-1.8 hr 1.25-2.9 hr 72 mins Metabolite enzyme CYP 3A4 、 CYP 2C8 CYP 2C9 (70%) 、 CYP 3A4(30%) CYP 2C9 ＜ 25% UGT 1A9, 1A3 (74%) Drug-drug interaction Gemfibrozil, macrolide, cyclosporine, -conazole, CCB, atorvastatin, simvastatin Warfarin, Phenytoin, Rosuvastatin, Fluvastatin No significant interaction Dose reduction with CYP3A4 inhibitors Yes No No Metabolites in urine 8-10 % 80-83 % 93 % (inactive) Metabolites in feces 80-90 % 8-12 % 7 % CKD stage 3,4 or Kidney transplant Initiate at 0.5mg (GFR ＜ 40mL/min/1.73m 2 Initiate at low dose: 60mg No dose adjustment necessary Dialysis Dosing Initiate at low dose Avoid Initiate at low dose Safety - hypoglycemia - GI intolerance 16-31 % 3 2-5 % 5.5 % 3.2 % 6.1 % 1 1.4 % Efficacy - HbA 1C (0.25-4 mg tid, 12 wks) 3 -1.7 % (120 mg tid, 24 weeks)3 - 0.7 % (5~10 mg tid, 52 weeks) - 1.5 % Weight gain (0.5~4mg tid, 16weeks) 4 +1.8Kg (60-120mg tid, 16weeks) +0.7Kg (10~20mg tid, 16 weeks)5 體重無影響 BNHI price 4.98 6.5 4.87 Daily cost 7.47 ~ 79.68 9.75~29.25 3.65 ~ 29.22
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Editor's Notes
This slide shows the glycaemic targets for management of type 2 diabetes by various organisations worldwide Numerous studies have demonstrated that tight glycaemic control significantly reduces the risk of microvascular diseases such as neuropathy and microangiopathy There is, however, some debate around how tight the glycaemic control should be and different diabetes associations advocate different targets, which are summarised in this slide The optimal control of both fasting and the postprandial glycaemia is essential for achieving HbA 1c goal Self-monitoring of blood glucose is currently the optimal method for assessing plasma glucose levels and its frequency should be individualised to each person’s treatment regimen and level of glycaemic control. References: 1. Nathan DM, et al. Diabetologia. 2009;52:17-30. 2. IDF - European Guidelines. 2007. Available at: http://www.idf.org/webdata/docs/Guideline_PMG_final.pdf. Accessed: 5 Oct 2009. 3. American College of Endocrinology. Endocr Pract. 2007;13 (Suppl. 1):1-68. 4. NICE clinical guideline 87, May 2009. Available from: http://www.nice.org.uk/nicemedia/pdf/CG87NICEGuideline.pdf. Accessed: 1 Oct 2009. 5. Matthaei S et al. German Diabetes Association guidelines. 2008. Available at: http://www.deutsche-diabetes-gesellschaft.de/redaktion/mitteilungen/leitlinien/Uebersicht_leitlinien_evidenzbasiert.php. Accessed: 5 Oct 2009.
