Johnson M D, Campbell L K, Campbell R K
College of Pharmacy, Washington State University, Spokane 99204, USA.
Ann Pharmacother. 1998 Mar;32(3):337-48. doi: 10.1345/aph.17046.
To introduce troglitazone (CS-045, Rezulin), a new oral antidiabetic agent and discuss its pharmacology, therapeutics, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy.
A MEDLINE database search was completed to identify relevant articles including reviews, recent studies and abstracts, and data from Parke-Davis.
Due to the small number of published human studies available, some data are derived from animal studies and abstracts of human studies. Studies and abstracts chosen summarize the clinical action of troglitazone in healthy volunteers, in subjects with impaired glucose tolerance, and in patients with diabetes mellitus. Three of the six published human studies used subjects in a placebo-controlled, multicenter, randomized environment (type 2 diabetic patients or obese subjects with insulin resistance).
All clinical trials available, including unpublished reports, were reviewed.
Troglitazone is the first member of a new class of medications, the thiazolidinediones, to be approved for clinical use. Troglitazone increases insulin sensitivity in skeletal muscle and in hepatic and adipose tissue. It has been shown to decrease hepatic glucose output while having no effect on stimulating insulin secretion from the pancreatic beta-cells. Its metabolic effects decrease fasting and postprandial hyperglycemia, insulin concentrations, and triglyceride concentrations, while increasing high-density lipoprotein concentrations. There is some evidence, based on short-term trials, that troglitazone causes only minimal decreases in glycosylated hemoglobin A1C (HbA1C) concentrations. Data suggest that troglitazone decreases impaired glucose tolerance in nondiabetic obese subjects and leads to a reduction in both systolic and diastolic blood pressure in hypertensive type 2 diabetes mellitus patients. Troglitazone has a mild adverse effect profile, with rare instances of abnormal liver function tests.
Troglitazone appears to be a safe, effective, and useful new agent in the treatment of insulin-requiring type 2 diabetes mellitus patients, although its HbA1C-lowering effects have been minimal in short-term trials, and its insulin dosage-reduction activity remains unclear. The Food and Drug Administration has also approved its use as monotherapy and in combination with sulfonylureas for patients with type 2 diabetes. It may have use in the treatment of patients with impaired glucose tolerance, but more clinical experience is needed before definitive conclusions can be made. The role of troglitazone therapy in diabetes mellitus and impaired glucose intolerance will continue to evolve as the results of studies and our clinical experience with this agent become available.
介绍新型口服抗糖尿病药物曲格列酮（CS - 045，Rezulin），并讨论其药理学、治疗学、药代动力学、给药指南、不良反应、药物相互作用及临床疗效。
完成了对MEDLINE数据库的检索，以识别相关文章，包括综述、近期研究和摘要，以及来自帕克 - 戴维斯公司的数据。
由于已发表的人体研究数量较少，部分数据来源于动物研究和人体研究的摘要。所选择的研究和摘要总结了曲格列酮在健康志愿者、糖耐量受损受试者及糖尿病患者中的临床作用。六项已发表的人体研究中有三项在安慰剂对照、多中心、随机环境下使用了受试者（2型糖尿病患者或有胰岛素抵抗的肥胖受试者）。
对所有可得的临床试验，包括未发表的报告进行了综述。
曲格列酮是新一类药物噻唑烷二酮类中首个被批准用于临床的药物。曲格列酮可增加骨骼肌、肝脏和脂肪组织中的胰岛素敏感性。已表明它可降低肝脏葡萄糖输出，而对刺激胰腺β细胞分泌胰岛素无作用。其代谢作用可降低空腹及餐后高血糖、胰岛素浓度和甘油三酯浓度，同时增加高密度脂蛋白浓度。基于短期试验有一些证据表明，曲格列酮仅使糖化血红蛋白A1C（HbA1C）浓度有极小程度的降低。数据表明，曲格列酮可降低非糖尿病肥胖受试者的糖耐量受损，并使2型糖尿病高血压患者的收缩压和舒张压均降低。曲格列酮的不良反应较轻，肝功能检查异常的情况罕见。
曲格列酮似乎是治疗需用胰岛素的2型糖尿病患者的一种安全、有效且有用的新药，尽管在短期试验中其降低HbA1C的作用极小，且其降低胰岛素剂量的活性仍不明确。美国食品药品监督管理局也已批准其作为2型糖尿病患者的单一疗法及与磺脲类药物联合使用。它可能对糖耐量受损患者的治疗有用，但在得出明确结论前还需要更多临床经验。随着研究结果及我们对该药物的临床经验的可得，曲格列酮治疗在糖尿病及糖耐量受损中的作用将继续演变。
