达格列净治疗糖尿病合并慢性心力衰竭的临床研究

杨顺昱 江戈 杨兰 易军 麦炜颐

【摘要】目的 探討达格列净治疗糖尿病合并慢性心力衰竭（CHF）临床疗效及对患者血清炎症因子的影响。方法 122例糖尿病合并CHF患者依简单随机数表法分为达格列净组与对照组各61例。在常规治疗CHF（ACEI或ARB、β受体阻滞剂、醛固酮拮抗剂联合应用治疗方案）基础上，对照组服用非钠-葡萄糖协同转运蛋白-2抑制剂降糖药，达格列净组为达格列净10 mg/d，

均治疗4个月。统计2组总有效率、治疗前后血糖指标 [空腹血糖（FPG）、餐后2 h血糖（2 hPG）、

GHbA1c]水平、心功能指标参数（LVEF、CO、SV、CI）、血清炎性因子（TNF-α、IL-1β、IL-6）水平、生活质量（MLHFQ）、6 min步行距离（6MWT）及评估不良反应发生率。结果 达格列净组治疗总有效率（95.08%）高于对照组（83.61%）（P < 0.05）;治疗后2组FPG、2 hPG、GHbA1c水平较治疗前降低，且达格列净组的改善程度优于对照组（P均 < 0.05）;治疗后2组LVEF、CO、CI、SV较治疗前增高，且达格列净组改善更显著（P均 < 0.05）;治疗后2组血清TNF-α、IL-1β、IL-6水平较治疗前降低，且达格列净组降低更明显（P均 < 0.05）;治疗后2组6MWT较治疗前增加，MLHFQ评分降低，且达格列净组改善更佳（P均 < 0.05）;达格列净组不良反应发生率（3.28%）与对照组（4.92%）比较差异无统计学意义（P > 0.05）。结论 常规基础上加达格列净治疗糖尿病合并CHF，可有效改善血糖控制效果，提高心功能，下调炎症因子，增加患者6MWT，提升生活质量，不增加不良反应发生风险。

【关键词】达格列净;糖尿病;心力衰竭;炎症因子;心功能

Clinical study of dagagliflozin in the treatment of diabetes mellitus complicated with chronic heart failure Yang Shunyu， Jiang Ge， Yang Lan， Yi Jun， Mai Weiyi. Department of Cardiology， Guilin Hospital of Chinese Traditional and Western Medicine，Guilin 541004， China

Corresponding author，Mai Weiyi，E-mail：  maiweiyi@mail.sysu.edu.cn

【Abstract】Objective To evaluate the clinical efficacy of dapagliflozin in the treatment of diabetes mellitus complicated with chronic heart failure （CHF）， and investigate the effect upon serum inflammatory factors. Methods 122 diabetes mellitus patients complicated with CHF were enrolled and randomly assigned into the dapagliflozin （n = 61） and control groups （n = 61） according to the simple random number table method. On the basis of conventional treatment of CHF （angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists， β-receptor blockers， and aldosterone antagonists）， patients in the control group received non-SGLT-2 inhibitors for 4 months， and those in the dapagliflozin group were given with 4-month dapagliflozin 10 mg/d. The total effective rate， blood glucose indexes before and after treatment （fasting blood glucose （FPG）， 2 h postprandial blood glucose （2 hPG） and GHbA1c levels）， cardiac function indexes （LVEF， CO， SV and CI）， serum inflammatory factors （ TNF-α， IL-1β and IL-6 levels）， quality of life （MLHFQ） and 6-min walk test （6MWT）， and the incidence of adverse reactions were statistically analyzed between two groups. Results The total effective rate in the dapagliflozin was 95.08%， higher than 83.61% in the control group （P < 0.05）. The FPG， 2 hPG and GHbA1c levels in two groups were declined after corresponding treatment， with a better improvement in the dapagliflozin group （all P < 0.05）. The LVEF， CO， CI and SV were elevated in two groups after corresponding interventions， with a better improvement in the dapagliflozin group （（LVEF： （56.71±5.61）% vs. （50.04±6.02）%）， （CO： 5.51±0.95 vs. 4.68±0.89 L/min）， （CI： 3.86±0.77 vs. 3.25±0.69 L/（min·m2）） and （SV： 82.32±8.09 vs. 77.07±7.81 ml）， all P < 0.05）. The serum levels of inflammatory factors （TNF-α， IL-1β and IL-6） were down-regulated in two groups， which were even lower in the dapagliflozin group（（TNF-α： 22.06±6.25 vs. 33.07±5.67 ng/L）， （IL-1β： 305.04±101.23 vs. 411.60±113.18 ng/L） and （IL-6： 79.71±16.35 vs. 96.63±18.38 ng/L）， all P < 0.05）. In two groups， the 6MWT was increased， whereas the MLHFQ score was decreased after corresponding therapies， with a better improvement in the dapagliflozin group （（6MWT： 419.86±38.59 vs. 365.61±32.29 m） and （MLHFQ score： 26.67±4.69 vs. 32.06±5.37）， both P < 0.05）. No statistical significance was observed in the incidence rate of adverse reactions between the dapagliflozin and control groups （3.28% vs. 4.92%， P > 0.05）. Conclusions Dapagliflozin treatment based on routine therapy can effectively improve heart function， control the blood glucose level， down-regulate the expression of inflammatory factors， extend the 6MWT， enhance the quality of life and does not increase the risk of adverse reactions in diabetes mellitus patients complicated with CHF.

【Key words】Dapagliflozin; Diabetes mellitus; Heart failure; Inflammatory factor; Heart function

慢性心力衰竭（CHF）为各种心脏功能性或结构性病症的终末阶段，虽传统常规规范治疗方案（ACEI或ARB、β受体阻滞剂、醛固酮拮抗剂联合治疗方案）有一定效果，但5年生存率仍较低[1-3]。……