恩格列净对非肥胖成人1型糖尿病患者血糖波动的影响:一项随机平行对照试验

Effects of empagliflozin on glycemic variability in non-obese adults with type 1 diabetes mellitus:a randomized and parallel controlled trial

目的探讨恩格列净联合胰岛素治疗对非肥胖成人1型糖尿病(T1DM)患者血糖波动的作用。方法本研究为前瞻性、随机对照、开放标签的临床研究。纳入2019年11月至2022年12月在中南大学湘雅二医院就诊的60例T1DM患者,按照SPSS 26.0软件生成的随机数将受试者以1∶1的比例随机分配,分别接受恩格列净联合胰岛素治疗(干预组)或胰岛素治疗(对照组)6个月,每组30例患者。主要结局指标为血糖波动情况,通过平均血糖波动幅度(MAGE)、血糖水平标准差(SD)和变异系数(CV)来评估血糖波动。次要结局指标为血糖控制情况,通过有效降糖率、糖化血红蛋白(HbA_(1c))水平、HbA_(1c)达标率、胰岛素日剂量、葡萄糖高于/低于/在目标范围内时间、血糖风险指数来评估血糖控制情况。通过低血糖事件和不良事件发生率评估安全性。HbA_(1c)降低>0.3%视为有效降糖。组间比较采用混合效应模型和广义估计方程,组内比较采用配对t检验。结果共有59例T1DM患者纳入分析,其中干预组29例,对照组30例,两组性别差异无统计学意义[男性占比分别为58.62%(17/29)和36.67%(11/30),P=0.091]。结果显示,干预组评估血糖波动指标与对照组相比差异无统计学意义(P>0.05)。干预组有效降糖率显著高于对照组[分别为61.54%(16/26)和28.00%(7/25),P=0.016]。安全性分析显示,两组患者低血糖的发生率差异无统计学意义[分别为85.71%(24/28)和81.48%(22/27),P=0.729];试验期间两组均未发生酮症酸中毒事件。结论恩格列净联合胰岛素治疗非肥胖T1DM患者的安全性良好,未明显增加低血糖和酮症酸中毒风险,可改善非肥胖成人T1DM患者的血糖控制,尚未观察到对血糖波动的有益作用。

Objective To investigate the effect of empagliflozin plus insulin on glucose variability in non-obese adults with type 1 diabetes mellitus(T1DM).Methods This study was a prospective,randomized controlled,and open-label clinical trial.From November 2019 to December 2022,a total of 60 non-obese adult patients with T1DM from the Second Xiangya Hospital of Central South University were enrolled.They were randomly assigned in a 1∶1 ratio using random numbers generated by SPSS 26.0 software to receive either empagliflozin combined with insulin(intervention group)or insulin alone(control group)for 6 months,with 30 patients in each group.The primary outcome indicator was glycemic variability,which was assessed by mean amplitude of glucose excursions(MAGE),standard deviation(SD),and coefficient variation(CV).The secondary outcome indicator was glycemic control,which was assessed by clinically meaningful glycated hemoglobin A 1c(HbA_(1c))reduction rate,HbA_(1c) level,the rate of achieving the HbA_(1c) target,daily insulin dose,time above/below/in range,and glycemia risk index.Safety was assessed based on the incidence of hypoglycemic events and adverse events.The clinically meaningful HbA_(1c) reduction was defined as a reduction in HbA_(1c) greater than 0.3%.A mixed-effects model and generalized estimating equation were used to compare between groups,and a paired t test was used to compare within groups.Results A total of 59 cases were included in the analysis,with 29 in the intervention group and 30 in the control group[male:58.62%(17/29)vs.36.67%(11/30),respectively,P=0.091].There was no significant difference between the intervention group and the control group in the glycemic variability indicators.The proportion of patients with a clinically meaningful reduction in HbA_(1c) was significantly higher in the intervention group than in the control group[61.54%(16/26)vs.28.00%(7/25),respectively,P=0.016].The safety analysis showed no significant difference in hypoglycemia between the two groups in non-obese adults with T1DM[85.71%(24/28)vs.81.48%(22/27),respectively,P=0.729],and no ketoacidosis events were reported during the trial.Conclusions Empagliflozin combined with insulin in non-obese T1DM patients was safe and did not significantly increase the risk of hypoglycemia and ketoacidosis.Empagliflozin may improve glycemic control status in non-obese patients with T1DM,and did not significantly improve glycemic variability in non-obese adults with T1DM.