Page 102 - 《中国药房》2021年第1期

Meta-analysis of Efficacy and Safety of SGLT-2 Inhibitors Combined with Insulin for Type 1 Diabetes
Mellitus
LUO Jie ，WANG Keke ，JIANG Mingyan （1. Dept. of Pharmacy，the First Affiliated Hospital of China
1
1，2
1，2
Medical University，Shenyang 110001，China；2. School of Pharmaceutical Science，China Medical University，
Shenyang 110122，China）
ABSTRACT OBJECTIVE：To systematically evaluate the efficacy and safety of sodium-glucose co-transporter 2 （SGLT-2）
inhibitors combined with insulin in the treatment of type 1 diabetes mellitus（T1DM），and to provide evidence-based reference for
clinical treatment of T1DM. METHODS：Retrieved from PubMed，Cochrane library，Embase，Clinical Trials，CNKI，CBM and
Wanfang database，randomized controlled trials（RCT）about SGLT-2 inhibitor（trial group）versus placebo（control group）in the
treatment of T1DM based on insulin treatment were collected during the inception to Feb. 2020. After data extraction of literatures
met inclusion criteria，Cochrane risk bias evaluation tool 5.1.0 was used to evaluate its quality，and Meta-analysis was perfomed by
using Stata 12.0 software. RESULTS：A total of 11 RCTs were included，involving 7 003 patients. The results of Meta-analysis
showed that the decrease of HbA1c [SMD＝－0.49，95％CI（－0.53，－0.44），P＜0.001]，the proportion of patients with HbA1c≥
0.5％ and without severe hypoglycemia [OR＝3.93，95％ CI（3.49，6.21），P＜0.001]，the proportion of patients with HbA1c≥
0.5％ [OR＝2.65，95％CI（2.25，3.12），P＜0.001]，the target rate of HbA1c level＜7.0％ [OR＝2.85，95％CI（2.44，3.33），P＜0.001]
and the decrease of body weight [SMD＝－0.83，95％CI（－0.96，－0.70），P＜0.001] in trial group were significantly larger or
higher than control group；the decrease values of daily insulin dosage，fasting blood glucose，postprandial blood glucose，systolic
blood pressure and diastolic blood pressure in trial group were significantly higher than those in the control group，with statistical
significance（P≤0.011）. The total incidence of ADR [OR＝1.14，95％CI（1.04，1.26），P＝0.007]，the incidence of SGLT-2 inhibitor
related ADR [OR＝2.17，95％CI（1.75，2.99），P＜0.001]，the incidence of severe ADR [OR＝1.48，95％CI（1.24，1.77），P＜0.001]，
the incidence of genital infection [OR＝3.84，95％CI（3.14，4.69），P＜0.001]，the incidence of diarrhea [OR＝1.47，95％CI（1.09，
1.97），P＝0.011]，the incidence of fluid reduction related ADR [OR＝2.05，95％CI（1.37，3.08），P＝0.001]，the incidence of ketosis
related ADR [OR＝4.18，95％CI（3.15，5.55），P＜0.001]，the incidence of ketoacidosis [OR＝4.33，95％CI（3.01，6.23），P＜0.001]
and the incidence of severe ketoacidosis [OR＝5.06，95％CI（2.61，9.81），P＜0.001] were significantly higher than control group，
with statistical significance. There was no statistical significance in the incidence of hypoglycemia，severe hypoglycemia，urinary
tract infection or kidney injury between 2 groups. CONCLUSIONS：SGLT-2 inhibitors for the treatment of T1DM can significantly
improve the blood glucose，reduce body weight and daily insulin dose，lower systolic blood pressure and diastolic blood pressure，
while dose not increase the risk of hypoglycemia，urinary tract infections and renal impairment but increase the risk of total ADR as
well as the risk of ADR such as genital infection，diarrhea，ketoacidosis，to which should be paid attention.
KEWORDS Sodium-glucose co-transporter 2 inhibitors；Type 1 diabetes mellitus；Glycosylated hemoglobin；Body weight；
Therapeutic efficacy；Safety；Meta-analysis

[4]
1型糖尿病（Type 1 diabetes mellitus，T1DM）是一种 用机制使其用于T1DM患者能同样获益 。但该类药有
由于内源性胰岛素绝对缺乏引起慢性高血糖和进行性 增加T2DM患者酮症风险的报道 [5-6] ，在T1DM患者中是
代谢紊乱的自身免疫性疾病 。目前，T1DM 在临床上 否会增加酮症及低血糖等的发生率仍需探讨。为了进
[1]
的主要治疗手段是胰岛素替代疗法，但胰岛素易造成低 一步探究SGLT-2抑制剂用于T1DM患者辅助治疗的疗
血糖和体质量增加等不良反应，患者依从性低，而且不 效与安全性，本研究筛选国内外 SGLT-2 抑制剂应用于
能阻止或延缓胰岛功能的进一步破坏，导致T1DM患者 T1DM 的随机对照试验（RCT）进行 Meta 分析，为临床
难以维持理想的血糖水平 [1-4] 。非胰岛素辅助降糖治疗 T1DM治疗提供循证参考。
通过其他机制降低血糖，可以减少低血糖及其他不良反 1 资料与方法
[1]
应的发生，增加患者依从性 。现在批准用于 T1DM 的 1.1 纳入与排除标准
非胰岛素辅助降糖治疗药物仍十分有限。钠-葡萄糖协 1.1.1 研究类型
同转运蛋白 2（Sodium-glucose co-transporter 2，SGLT-2） RCT，无论是否采用盲法均纳入研究，语种限定为
抑制剂（如坎格列净、卡格列净、达格列净、恩格列净、依 中文和英文。
格列净、鲁格列净、托格列净、雷莫列净、舍格列净、索格 1.1.2 研究对象
列净、埃格列净等）可通过抑制肾脏中葡萄糖的重吸收， T1DM患者，需符合1997年美国糖尿病协会（ADA）
[2]
增加尿糖排出从而达到降低血糖的作用 ，该类药在多 糖尿病诊断标准或1998年世界卫生组织（WHO）糖尿病
[3]
个国家已批准上市用于2型糖尿病（T2DM）治疗 ，其作 诊断标准；患者性别不限，年龄≥18岁。

·92 · China Pharmacy 2021 Vol. 32 No. 1 中国药房 2021年第32卷第1期