Médecine Interne et Diabétologie, Centre Hospitalier Sud Francilien, Corbeil Essonnes, France.
Diabetes Obes Metab. 2009 Sep;11(9):844-54. doi: 10.1111/j.1463-1326.2009.01055.x. Epub 2009 Jul 13.
This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide.
This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA(1c)) <or=6.5%] or titrated up to 45 mg (if HbA(1c) >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA(1c) (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B) were calculated.
Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA(1c) and -2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA(1c) level of <8.5% achieved the HbA(1c) target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA(1c) level was >or= 8.5%, 13% achieved the HbA(1c) target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group.
In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA(1c), FPG and surrogate measures of beta-cell function. Patients were more likely to reach target HbA(1c) levels (< 7.0%) with pioglitazone treatment if their baseline HbA(1c) levels were < 8.5%, highlighting the importance of early triple therapy.
本研究评估了在二甲双胍和磺酰脲或格列奈控制不佳的 2 型糖尿病患者中，添加吡格列酮与安慰剂相比的疗效。
这项多中心、双盲、平行组研究将 299 例 2 型糖尿病患者随机分为两组，分别接受吡格列酮 30mg/天或安慰剂治疗 3 个月。在这段时间后，患者继续接受吡格列酮治疗，剂量为 30mg[如果糖化血红蛋白 A1c（HbA1c）≤6.5%]或滴定至 45mg（如果 HbA1c＞6.5%），或安慰剂再治疗 4 个月。主要疗效终点为 HbA1c（百分比变化）的改善。次要终点包括空腹血糖（FPG）、胰岛素、C 肽、胰岛素原和血脂的变化。计算胰岛素原/胰岛素比值以及稳态模型评估的胰岛素抵抗（HOMA-IR）和胰岛β细胞功能的稳态模型评估（HOMA-B）。
在二甲双胍和磺酰脲或格列奈联合治疗失败的基础上加用吡格列酮治疗，与加用安慰剂相比，血糖控制有统计学意义上的显著改善。经过 7 个月的三联治疗，HbA1c 组间差异为 1.18%，FPG 为-2.56mmol/l（p＜0.001）。在吡格列酮组中，基线 HbA1c 水平＜8.5%的患者中，有近一半（44.4%）在最终就诊时达到了 HbA1c＜7.0%的目标，而安慰剂组为 4.9%。当基线 HbA1c 水平≥8.5%时，吡格列酮组中有 13%达到了 HbA1c＜7.0%的目标，而安慰剂组中没有。与安慰剂组相比，吡格列酮组的 HOMA-IR、胰岛素、胰岛素原和 C 肽降低，HOMA-B 升高。
在联合治疗效果不佳的患者中，早期添加吡格列酮可改善 HbA1c、FPG 和胰岛β细胞功能的替代指标。如果患者的基线 HbA1c 水平＜8.5%，则更有可能通过吡格列酮治疗达到目标 HbA1c 水平（＜7.0%），这突出了早期三联治疗的重要性。
