吡格列酮对2型糖尿病患者血糖控制及致动脉粥样硬化性血脂异常的影响。

The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus.

作者信息

Rosenblatt S, Miskin B, Glazer N B, Prince M J, Robertson K E

机构信息

Irvine Clinical Research Center, California, USA.

出版信息

Coron Artery Dis. 2001 Aug;12(5):413-23. doi: 10.1097/00019501-200108000-00011.

DOI:10.1097/00019501-200108000-00011

PMID:11491207

Abstract

BACKGROUND

To evaluate the glycemic control, lipid effects, and safety of pioglitazone in patients with type 2 diabetes mellitus.

DESIGN AND METHODS

Patients (n = 197) with type 2 diabetes mellitus, a hemoglobin A1c (HbA1c) > or = 8.0%, fasting plasma glucose (FPG) > 7.7 mmol/l (140 mg/dl), and C-peptide > 0.331 nmol/l (1 ng/ml) were enrolled in this 23-week multi-center (27 sites), double-blind clinical trial and randomized to receive either a placebo or pioglitazone HCl 30 mg (pioglitazone), administered once daily, as monotherapy. Patients were required to discontinue all anti-diabetic medications 6 weeks before receiving study treatment. Efficacy parameters included HbA1c fasting plasma glucose (FPG), serum C-peptide, insulin, triglycerides (Tg), and cholesterol (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C]). Adverse event rates, serum chemistry, and physical examinations were recorded.

RESULTS

Compared with placebo, pioglitazone significantly (P= 0.0001) reduced HbA1c (-1.37% points), FPG (-3.19 mmol/l; -57.5 mg/dl), fasting C-peptide (-0.076+/-0.022 nmol/l), and fasting insulin (-11.88+/-4.70 pmol/l). Pioglitazone significantly (P < 0.001) decreased insulin resistance (HOMA-IR; -12.4+/-7.46%) and improved beta-cell function (Homeostasis Model Assessment (HOMA-BCF); +47.7+/-11.58%). Compared with placebo, fasting serum Tg concentrations decreased (-16.6%; P = 0.0178) and HDL-C concentrations increased (+12.6%; P= 0.0065) with pioglitazone as monotherapy. Total cholesterol and LDL-C changes were not different from placebo. The overall adverse event profile of pioglitazone was similar to that of placebo, with no evidence of drug-induced elevations of serum alanine transaminase (ALT) concentrations or hepatotoxicity.

CONCLUSIONS

Pioglitazone improved insulin resistance and glycemic control, as well as Tg and HDL-C - which suggests that pioglitazone may reduce cardiovascular risk for patients with type 2 diabetes.

摘要

背景

评估吡格列酮对2型糖尿病患者血糖控制、血脂影响及安全性。

设计与方法

197例2型糖尿病患者，糖化血红蛋白（HbA1c）≥8.0%，空腹血糖（FPG）>7.7 mmol/l（140 mg/dl），C肽>0.331 nmol/l（1 ng/ml），纳入这项为期23周的多中心（27个地点）双盲临床试验，随机接受安慰剂或盐酸吡格列酮30 mg（吡格列酮），每日一次，作为单一疗法。患者在接受研究治疗前6周需停用所有抗糖尿病药物。疗效参数包括HbA1c、空腹血糖（FPG）、血清C肽、胰岛素、甘油三酯（Tg）和胆固醇（总胆固醇[TC]、高密度脂蛋白胆固醇[HDL-C]、低密度脂蛋白胆固醇[LDL-C]）。记录不良事件发生率、血清化学指标和体格检查结果。

结果

与安慰剂相比，吡格列酮显著（P = 0.0001）降低HbA1c（-1.37个百分点）、FPG（-3.19 mmol/l；-57.5 mg/dl）、空腹C肽（-0.076±0.022 nmol/l）和空腹胰岛素（-11.88±4.70 pmol/l）。吡格列酮显著（P < 0.001）降低胰岛素抵抗（HOMA-IR；-12.4±7.46%）并改善β细胞功能（稳态模型评估（HOMA-BCF）；+47.7±11.58%）。与安慰剂相比，作为单一疗法的吡格列酮使空腹血清Tg浓度降低（-16.6%；P = 0.0178），HDL-C浓度升高（+12.6%；P = 0.0065）。总胆固醇和LDL-C变化与安慰剂无差异。吡格列酮的总体不良事件情况与安慰剂相似，没有证据表明药物引起血清丙氨酸转氨酶（ALT）浓度升高或肝毒性。