Eurich Dean T, Tsuyuki Ross T, Majumdar Sumit R, McAlister Finlay A, Lewanczuk Richard, Shibata Marcelo C, Johnson Jeffrey A
School of Public Health, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada.
Trials. 2009 Feb 9;10:12. doi: 10.1186/1745-6215-10-12.
Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.
The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.
Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.
Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.
ClinicalTrials.gov Identifier: NCT00325910.
二甲双胍在糖尿病合并心力衰竭（HF）患者中有“黑框”禁忌证，但许多人认为它是这种情况下的首选治疗药物。因此，我们试图开展一项初步研究，以评估进行一项具有临床终点的大型随机对照试验的可行性。
该初步研究是一项随机双盲安慰剂对照试验。在加拿大艾伯塔省埃德蒙顿市的医院和心力衰竭诊所对HF合并2型糖尿病患者进行筛查（人口约100万）。主要排除标准包括当前使用胰岛素或高剂量二甲双胍、肾功能下降或糖化血红蛋白<7%。患者将被随机分为每日服用1500毫克二甲双胍或匹配的安慰剂，并随访6个月，观察各种功能结局以及临床事件。
在6个月期间筛查了58例患者，所有患者均被排除。由于入组无效，该初步研究被放弃。筛查患者的平均年龄为77（标准差9）岁，57%为男性。排除的主要原因是：使用胰岛素治疗（n = 23；40%）、糖化血红蛋白<7%（n = 17；29%）和当前使用高剂量二甲双胍（n = 12；21%）。总体而言，禁忌的二甲双胍治疗是最常用的口服降糖药（n = 27；51%）。患者平均每天服用1706毫克（标准差488毫克）二甲双胍，12例（44%）仅使用二甲双胍。
尽管科学文献中存在不确定性，但二甲双胍在HF中的安全性或有效性似乎不存在临床不确定性，这使得进行确定性的随机试验几乎不可能。
ClinicalTrials.gov标识符：NCT00325910。
