Kooy Adriaan, de Jager Jolien, Lehert Philippe, Bets Daniël, Wulffelé Michiel G, Donker Ab J M, Stehouwer Coen D A
Department of Internal Medicine and Bethesda Diabetes Research Center, RA Hoogeveen, the Netherlands.
Arch Intern Med. 2009 Mar 23;169(6):616-25. doi: 10.1001/archinternmed.2009.20.
We investigated whether metformin hydrochloride has sustained beneficial metabolic and (cardio) vascular effects in patients with type 2 diabetes mellitus (DM2).
We studied 390 patients treated with insulin in the outpatient clinics of 3 hospitals in a randomized, placebo-controlled trial with a follow-up period of 4.3 years. Either metformin hydrochloride, 850 mg, or placebo (1-3 times daily) was added to insulin therapy. The primary end point was an aggregate of microvascular and macrovascular morbidity and mortality. The secondary end points were microvascular and macrovascular morbidity and mortality, as separate aggregate scores. In addition, effects on hemoglobin A(1c) (HbA(1c)), insulin requirement, lipid levels, blood pressure, body weight, and body mass index were analyzed.
Metformin treatment prevented weight gain (mean weight gain, -3.07 kg [range, -3.85 to -2.28 kg]; P < .001), improved glycemic control (mean reduction in HbA(1c) level, 0.4% percentage point [95% CI, 0.55-0.25]; P < .001) (where CI indicates confidence interval), despite the aim of similar glycemic control in both groups, and reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P < .001). Metformin was not associated with an improvement in the primary end point. It was, however, associated with an improvement in the secondary, macrovascular end point (hazard ratio, 0.61 (95% CI, 0.40-0.94; P = .02), which was partly explained by the difference in weight. The number needed to treat to prevent 1 macrovascular end point was 16.1 (95% CI, 9.2-66.6).
Metformin, added to insulin in patients with DM2, improved body weight, glycemic control, and insulin requirements but did not improve the primary end point. Metformin did, however, reduce the risk of macrovascular disease after a follow-up period of 4.3 years. These sustained beneficial effects support the policy to continue metformin treatment after the introduction of insulin in any patient with DM2, unless contraindicated. Trial Registration ClinicalTrials.gov Identifier: NCT00375388.
我们研究了盐酸二甲双胍对2型糖尿病（DM2）患者是否具有持续有益的代谢及（心脏）血管效应。
我们在3家医院的门诊对390例接受胰岛素治疗的患者进行了一项随机、安慰剂对照试验，随访期为4.3年。在胰岛素治疗基础上加用850毫克盐酸二甲双胍或安慰剂（每日1 - 3次）。主要终点是微血管和大血管发病及死亡的综合情况。次要终点是微血管和大血管发病及死亡情况，分别作为综合评分。此外，分析了对糖化血红蛋白（HbA1c）、胰岛素需求量、血脂水平、血压、体重和体重指数的影响。
二甲双胍治疗可防止体重增加（平均体重增加，-3.07千克[范围，-3.85至-2.28千克]；P <.001），改善血糖控制（HbA1c水平平均降低0.4个百分点[95%可信区间，0.55 - 0.25]；P <.001）（其中CI表示可信区间），尽管两组血糖控制目标相似，且降低了胰岛素需求量（平均降低19.63国际单位/天[95%可信区间，24.91 - 14.36国际单位/天]；P <.001）。二甲双胍与主要终点的改善无关。然而，它与次要的大血管终点的改善有关（风险比，0.61[95%可信区间，0.40 - 0.94；P =.02]），这部分可由体重差异解释。预防1例大血管终点所需治疗人数为16.1（95%可信区间，9.2 - 66.6）。
在DM2患者的胰岛素治疗中加用二甲双胍，可改善体重、血糖控制和胰岛素需求量，但未改善主要终点。然而，二甲双胍在4.3年的随访期后降低了大血管疾病风险。这些持续的有益效应支持在任何DM（2）患者开始胰岛素治疗后继续使用二甲双胍治疗的策略，除非有禁忌证。试验注册ClinicalTrials.gov标识符：NCT003
