恩格列净联合胰岛素短期强化治疗2型糖尿病患者的疗效和安全性:一项前瞻、随机、开放、平行对照的临床研究

Efficacy and safety of empagliflozin in combination with short-term intensive insulin therapy in patients with type 2 diabetes mellitus:a prospective,open-label,parallel-controlled randomized clinical trial

目的探讨恩格列净联合胰岛素短期强化治疗对血糖不达标的2型糖尿病(T2DM)患者的临床疗效及安全性。方法选取2019年4月至2021年3月于河北医科大学第二医院内分泌科住院并需要接受基础加餐时4针胰岛素强化治疗的T2DM患者。采用随机数字表法将其随机分为恩格列净联合胰岛素短期强化治疗(EMPA)组和单纯胰岛素(门冬胰岛素+德谷胰岛素)短期强化治疗(Con)组。记录两组患者治疗14 d前、后空腹血糖(FPG)、糖化白蛋白(GA)、葡萄糖在目标范围内时间(TIR)及血糖波动相关指标[平均血糖波动幅度(MAGE)、血糖标准差(SDBG)、最大血糖波动幅度(LAGE)、日间血糖平均绝对差(MODD)]等, 并记录两组患者血糖达标时间、每日胰岛素用量和低血糖发生情况等。组间比较采用t检验、t′检验、Mann‐WhitneyU检验、χ^(2)检验或Fisher确切概率法, 组内比较采用配对t检验。结果最终完成试验患者共60例, 其中EMPA组30例, Con组30例。治疗14 d后, EMPA组和Con组FPG较治疗前分别下降(6.10±3.03)和(5.79±3.90)mmol/L, GA较治疗前分别下降(7.17±2.81)%和(6.95±3.45)%, 治疗后两组FPG、GA的变化值差异均无统计学意义(P>0.05)。治疗14 d后, EMPA组的TIR、SDBG、LAGE明显优于Con组, 差异均有统计学意义(P<0.05)。EMPA组和Con组的血糖达标时间分别为(4.2±1.4)和(6.7±1.9)d, 门冬胰岛素平均用量分别为(17.7±5.8)和(21.4±7.8)U/d, 德谷胰岛素平均用量分别为(12.3±4.0)和(15.1±5.2)U/d, 差异均有统计学意义(P<0.05)。EMPA组和Con组的低血糖发生率分别为6.67%(2/30)和3.33%(1/30), 差异无统计学意义(P>0.05)。结论恩格列净联合胰岛素短期强化治疗不仅能有效控制血糖水平, 缩短血糖达标时间, 而且能同时降低血糖波动幅度, 减少胰岛素用量, 且安全性良好。

Objective To evaluate the clinical efficacy and safety of empagliflozin combined with short-term intensive insulin therapy in patients with type 2 diabetes mellitus(T2DM)who have poor glycemic control.Methods Patients who were hospitalized in the Endocrinology Department of the Second Hospital of Hebei Medical University from April 2019 to March 2021 were included in this clinical trial.T2DM patients expected to receive basal and prandial insulin injections(four times a day)were randomly assigned to two groups using a random number table.The observation group(EMPA group)was given empagliflozin plus short-term intensive insulin therapy and the control group(Con group)was given only short-term intensive insulin therapy.Patients in Con group were treated with four subcutaneous injections of insulin aspart plus insulin degludec daily.In the EMPA group,on the basis treatment of Con group,the empagliflozin was given 10 mg each time,q.d.,orally in the morning.The change in fasting blood glucose(FPG),glycated albumin(GA),time in range(TIR)and blood glucose fluctuation indicators[mean amplitude of glucose excursions(MAGE),the standard deviation of blood glucose level(SDBG),largest amplitude of glycaemic excursions(LAGE),absolute mean daily difference(MODD)]were recorded and compared.The time of reaching the standard blood glucose,daily insulin dosage and the occurrence of hypoglycemia in both groups were also recorded and compared.The t test,t′test,Mann‐Whitney U test,chi-square test or Fisher exact probability test were used for comparison between groups and paired t test was used for intra-group comparison.Results A total of 60 patients completed the trial,including 30 in the EMPA group and 30 in the Con group.After 14 days of treatment,FPG reduced(6.10±3.03)mmol/L and(5.79±3.90)mmol/L,at the same time,GA reduced(7.17±2.81)%and(6.95±3.45)%from baseline respectively in EMPA group and Con group.However,there was no statistically significant difference in the changes of FPG and GA between two groups(P>0.05).TIR,SDBG and LAGE of the EMPA group were significantly lower than those indicators of the Con group after 14 days treatment,and the difference were statistically significant(P<0.05).The time of reaching standard blood glucose in EMPA group and Con group were(4.2±1.4)d and(6.7±1.9)d,respectively.The average insulin aspart dosage was(17.7±5.8)U/d and(21.4±7.8)U/d,and the average dosage of insulin degludec was(12.3±4.0)U/d and(15.1±5.2)U/d in EMPA group and Con group,respectively.These differences were statistically significant(P<0.05).The incidence of hypoglycemia in EMPA group and Con group was 6.67%(2/30)and 3.33%(1/30),and the difference was not statistically significant(P>0.05).Conclusions Empagliflozin combined with short-term intensive insulin therapy could control blood glucose levels and shorten the time for reaching target effectively.This therapy could also reduce blood glucose fluctuations and the amount of insulin,and has good safety.