- 學位論文
臺大醫院thiazolidinediones類藥物使用型態之回溯性分析
A Retrospective Drug Utilization Analysis of Thiazolidinediones in National Taiwan University Hospital
並列摘要
The thiazolidinediones (TZDs) are a new class of compounds for treatment of type 2 diabetes by decreasing insulin resistance. The first one of TZDs, troglitazone, was withdrawn from the market in the March 2000 because it caused severe idiosyncratic liver injury. Rosiglitazone and pioglitazone are being marketed as safe alternatives and periodic liver enzyme monitoring is also recommended in view of the experience of troglitazone. Since Taiwan is an endemic area of viral hepatitis, the prevalence of drug induced hepatotoxicity may be different from that of the other countries. A retrospective review of medical records was carried out to evaluate the practice of liver enzyme monitor and the prevalence of abnormal liver function during TZDs therapy and the utilizing pattern of TZDs was also explored. A total of 364 patients, who were diagnosed as type 2 diabetes and initiated with rosiglitazone in National Taiwan University hospital during the period from Oct 2001 to Dec 2001, were included. The mean age was 61.4 years old and the mean duration of diagnosed diabetes was 8.87 years. Baseline mean HbA1C and FPG were 9.2% and 205.3 mg/dL, respectively. Lack of efficacy of previous medical therapy was the most common reason for initiation of TZDs. Mean rosiglitazone daily dose was 4.9 mg which was lower than the maximal recommended dose. The most common antidiabetic regimen was rosiglitazone in combination with sulfonylureas and metformin. Liver enzyme activity (ALT) was checked in 46.70% of patients before initiation of rosiglitazone, in which 8 patients (2.2%) were found to have a baseline ALT value higher than 2.5 times of the upper limit of normal. After rosiglitazone therapy, ALT >3 times the upper limit of normal was found in 9 patients (2.47%). Other major adverse drug reactions were edema (15.38%) and body weight gain (19.78%). Another 227 patients who were diagnosed as type 2 diabetes and initiated with pioglitazone in the same hospital during the period from May 2002 to Aug 2002 were also included. The mean age was 61.8 years old and the mean duration of diagnosed diabetes was 10.31 years in this group. Baseline mean HbA1C and FPG were 8.56% and 196.6 mg/dL, respectively. Lack of efficacy of previous medical therapy was the most common reason for initiation of TZDs. However, it was observed 47.35% of the patients had previous exposure to rosiglitazone. The most common antidiabetic regimen was pioglitazone in combination with sulfonylureas and metformin. Liver enzyme activity (ALT) was checked in 50.22% of patients before initiation of pioglitazone, in which 4 patients (1.76%) were found to have a baseline ALT value higher than 2.5 times of the upper limit of normal. After pioglitazone therapy, ALT >3 times the upper limit of normal was found in 5 patients (2.2%). The total incidences of edema and body weight gain were 18.5% and 33.92%, respectively. After one year’s observation, rosiglitazone and pioglitazone both could maintain the value of HbA1C around 7~8%. Since the exact mechanism of TZDs induced hepatotoxicity was not yet clearly understood, patients with underlying liver disease were evaluated as a risk factor in the study. ALT value higher then 3 times of the upper limit of normal was significantly related to patients’ underlying liver diseases by chi-square test. In conclusion, screening of underlying liver disease is recommended before initiation of TZDs in order to avoid hepatotoxicity related to TZDs.