Lapina Iu V, Narusov O Iu, Mareev V Iu, Bolotina M G, Shestakova M V, Masenko V P, Litonova G N, Arzamastseva N E, Baklanova N A, Belenkov Iu N
Institute of Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.
Kardiologiia. 2008;48(3):58-68.
Aim of the investigation was to study safety of therapy with metformin and its effect on clinical, hemodynamic, functional and neurohumoral status in patients with chronic heart failure and type 2 diabetes mellitus DM). Eighty one patients with light and moderate NYHA functional class (FC) II-III CHF, left ventricular ejection fraction < 45%, and DM were examined. As a result of randomization 2 groups were formed: with active (n=41) and usual (n=40) treatment. In active group with achievement of target levels of glycemia 24 (59%) patients were on oral hypoglicemic drags, 17 (41) patients received. All patients were on basal therapy of CHF. Initially efficacy and safety of metformin was investigated in a cohort of active treatment (jn metformin n=29, control n=12), including patients who were prescribed metformin not for the whole period. In addition in active group analysis was carried out among patients, who continually were treated with metformin for 12 months (n=30) in comparison with patients never treated with metformin (n=8). Total duration of the period of treatment and supervision was 12 months. Control examination was conducted before randomization, after 6 months of treatment, at the end of the study and included assessment of clunico-functional status of patients, renal function (GFR), neurohumoral profile (MNUP, NA, AII). The state of carbohydrate metabolism was assessed with the help of determination of HBA1C level and test with nutritional load given as of common breakfast -- 2-3 in the course of which fasting and postprandial level (in 2 hours after breakfast) of glucose (GLC), and fasting insulin and C-peptide. Overall safety of metformin was confirmed -- throughout whole period of follow up with different variants of comparative analysis no cases of lactic acidosis were revealed. Practical lack of positive influence of metformin on glycemia at its initially not high level was accompanied with improvement of FC CHF, parameters of central hemodynamics, augmentation of functional capacities of patients, improvement of quality of life, lowering of number of decompensations of CHF and diminishment of degree of activation of SAS. It can be suggested that this dynamics is conditioned by the presence of cardioprotective properties in metformin what allows to recommend its application in patients with CHF and type 2 DM.
本研究的目的是探讨二甲双胍治疗的安全性及其对慢性心力衰竭合并2型糖尿病患者的临床、血流动力学、功能和神经体液状态的影响。对81例纽约心脏病协会（NYHA）心功能分级为II-III级、左心室射血分数<45%且患有糖尿病的轻、中度心力衰竭患者进行了检查。随机分组后形成两组：积极治疗组（n=41）和常规治疗组（n=40）。在积极治疗组中，血糖达到目标水平的24例（59%）患者口服降糖药，17例（41%）患者接受胰岛素治疗。所有患者均接受心力衰竭的基础治疗。最初在积极治疗队列中（二甲双胍组n=29，对照组n=12）研究二甲双胍的疗效和安全性，其中包括未全程使用二甲双胍的患者。此外，在积极治疗组中，对持续使用二甲双胍12个月的患者（n=30）与从未使用过二甲双胍的患者（n=8）进行了分析。治疗和监测的总时长为12个月。在随机分组前、治疗6个月后、研究结束时进行对照检查，包括评估患者的临床功能状态、肾功能（肾小球滤过率）、神经体液指标（去甲肾上腺素、肾上腺素、血管紧张素II）。通过测定糖化血红蛋白水平以及进行普通早餐后的营养负荷试验来评估碳水化合物代谢状态，在试验过程中检测空腹和餐后2小时血糖、空腹胰岛素和C肽水平。二甲双胍的总体安全性得到证实——在整个随访期间，不同比较分析均未发现乳酸酸中毒病例。二甲双胍在初始水平不高时对血糖实际缺乏积极影响，但同时伴有心力衰竭心功能分级的改善、中心血流动力学参数的改善、患者功能能力的增强、生活质量的提高、心力衰竭失代偿次数的减少以及交感神经系统激活程度的降低。可以认为，这种动态变化是由二甲双胍的心脏保护特性所致，这使得推荐其应用于心力衰竭合并2型糖尿病患者。
