Prescrire Int. 2005 Aug;14(78):133-9.
(1) When single-agent therapy provides inadequate glycaemic control for patients with type 2 diabetes, most guidelines recommend metformin in combination with a glucose-lowering sulphonylurea as standard treatment, despite the lack of any proven impact on morbidity or mortality. Other options include switching to insulin or abandoning the target of strict glycaemic control. (2) Pioglitazone and rosiglitazone are approved for use in combination with a glucose-lowering sulphonylurea when metformin is poorly tolerated or contraindicated, and in combination with metformin in overweight patients. (3) A fixed-dose combination containing 1 or 2 mg of rosiglitazone plus 500 mg of metformin (hydrochloride) was launched onto the French market in October 2004. (4) The indication for rosiglitazone was extended to include its use as triple-agent therapy in combination with metformin and a glucose-lowering sulphonylurea. (5) No clinical trials assessing effects on mortality or morbidity have evaluated rosiglitazone or pioglitazone in combination with other oral antidiabetic drugs. (6) Several trials have compared the glucose-lowering effects of dual-agent therapy using rosiglitazone or pioglitazone plus a glucose-lowering sulphonylurea or metformin versus dual-agent therapy with metformin and a glucose-lowering sulphonylurea. (7) These clinical trials indicate that in terms of HbA1c level, dual-agent therapy based on rosiglitazone or pioglitazone is about as effective as combination therapy with metformin plus a glucose-lowering sulphonylurea. (8) The main known adverse effect of pioglitazone and rosiglitazone is water-sodium retention, which can provoke oedema and haemodilution anaemia, and can aggravate or reveal heart failure. (9) Pioglitazone has a positive effect on the lipid profile, whereas rosiglitazone increases the LDL-cholesterol level. (10) Dual-agent therapy with pioglitazone and a sulphonylurea causes more weight gain than metformin plus a sulphonylurea. (11) Several trials have assessed triple-agent regimens containing a glitazone. Three placebo-controlled double-blind trials have tested pioglitazone (one trial, nearly 300 patients) or rosiglitazone (two trials, about 1200 patients) for 12 to 26 weeks in patients whose glycaemia was poorly controlled by dual-agent therapy with a sulphonylurea plus metformin. The glycated haemoglobin level fell by 0.3% to 1.1% (in absolute values), depending on the trial and the dosage, but at a cost of the usual adverse effects such as weight gain, anaemia and oedema. Three unblinded trials have compared oral triple-agent regimens containing glitazone versus insulin plus metformin, alone or in combination with a glucose-lowering sulphonylurea; the treatment including glitazone was no more effective in terms of the glycated haemoglobin level, but was associated with an increase in adverse effects and dropouts. (12) Given the limited clinical data available in early 2005, pioglitazone and rosiglitazone have no place in the management of type 2 diabetes.
(1) 对于2型糖尿病患者，若单药治疗血糖控制不佳，多数指南推荐二甲双胍联合降糖磺脲类药物作为标准治疗方案，尽管尚无证据表明其对发病率或死亡率有影响。其他选择包括改用胰岛素或放弃严格血糖控制目标。(2) 当二甲双胍耐受性差或禁忌时，吡格列酮和罗格列酮被批准与降糖磺脲类药物联合使用，在超重患者中可与二甲双胍联合使用。(3) 一种含1或2毫克罗格列酮加500毫克二甲双胍（盐酸盐）的固定剂量复方制剂于2004年10月在法国上市。(4) 罗格列酮的适应证扩大到包括与二甲双胍和降糖磺脲类药物联合用作三联治疗。(5) 尚无评估罗格列酮或吡格列酮与其他口服抗糖尿病药物联合使用对死亡率或发病率影响的临床试验。(6) 多项试验比较了使用罗格列酮或吡格列酮加降糖磺脲类药物或二甲双胍的双联治疗与二甲双胍和降糖磺脲类药物双联治疗的降糖效果。(7) 这些临床试验表明，就糖化血红蛋白水平而言，基于罗格列酮或吡格列酮的双联治疗与二甲双胍加降糖磺脲类药物联合治疗效果相当。(8) 吡格列酮和罗格列酮已知的主要不良反应是水钠潴留，可引发水肿和稀释性贫血，并可加重或暴露心力衰竭。(9) 吡格列酮对血脂谱有积极作用，而罗格列酮会升高低密度脂蛋白胆固醇水平。(10) 吡格列酮与磺脲类药物的双联治疗比二甲双胍与磺脲类药物的双联治疗导致更多体重增加。(11) 多项试验评估了含格列酮类药物的三联治疗方案。三项安慰剂对照双盲试验在磺脲类药物加二甲双胍双联治疗血糖控制不佳的患者中，对吡格列酮（一项试验，近300例患者）或罗格列酮（两项试验，约1200例患者）进行了12至26周的测试。糖化血红蛋白水平绝对值下降了0.3%至1.1%，具体取决于试验和剂量，但代价是出现体重增加、贫血和水肿等常见不良反应。三项非盲试验比较了含格列酮类药物的口服三联治疗方案与胰岛素加二甲双胍，单独或与降糖磺脲类药物联合使用；就糖化血红蛋白水平而言，含格列酮类药物的治疗效果并不更好，但不良反应和退出率增加。(12) 鉴于2005年初可用的临床数据有限，吡格列酮和罗格列酮在2型糖尿病管理中没有地位。
