Safety and efficacy of sodium glucose co-transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta-analysis of randomized controlled trials

J Diabetes. 2019 Aug;11(8):645-655. doi: 10.1111/1753-0407.12890. Epub 2019 Jan 31.

Abstract

Background: The safety and efficacy of sodium glucose co-transporter 2 (SGLT2) inhibitors in a dose-dependent manner for type 1 diabetes mellitus (T1DM) are unclear.

Methods: Randomized clinical trials (RCT) were searched from PubMed, EMBASE, the Cochrane Library, Web of Science and ClinicalTrials until August 2018.

Results: Thirteen RCT with 5397 participants were included. SGLT2 inhibitors were proved to be effective in glycemic control and weight loss in T1DM. In the subgroups of different doses, SGLT2 inhibitors exhibited reductions in glycated haemoglobin, bodyweight, fasting plasma glucose, mean daily glucose, basal insulin dose, bolus insulin dose, estimated glomerular filtration rate and systolic blood pressure, and elevations in the mean amplitude of glucose excursions, and percentage of time in target glucose range in a dose-dependent manner. Reductions in total insulin dose and urinary glucose excretion were dose-independent. SGLT2 inhibitors did not induce hypoglycemia, severe hypoglycemia, cardiovascular events, bone fracture and all-cause mortality, but increased the risk of adverse events (AE), adverse events related to the drug treatment, infections, diabetic ketoacidosis (DKA) and renal disease correlated with dosage.

Conclusions: SGLT2 inhibitors in high and moderate doses can achieve a better outcome on efficacy, but may induce a higher risk of adverse events, especially DKA.

背景: 目前还不清楚葡萄糖协同转运体2(sodium glucose co-transporter 2,SGLT2)抑制剂对1型糖尿病的治疗是否为剂量依赖性。 方法: 从PubMed、EMBASE、the Cochrane Library、Web of Science和ClinicalTails搜集截至2018年8月份的随机对照试验(randomized clinical trials,RCT)。 结果: 本研究共纳入13个RCTs,包括5397名参与者。SGLT2抑制剂被证实对于1型糖尿病在血糖控制和减轻体重方面都是有效的。在不同剂量的亚组中,SGLT2抑制剂对糖化血红蛋白、体重、空腹血糖、日均血糖、基础胰岛素剂量、单剂胰岛素量、肾小球滤过率、收缩压都有降低作用,对平均血糖波动幅度和目标血糖范围内的时间百分比呈现剂量依赖性升高的特点,对总胰岛素剂量和尿糖排出量呈现非剂量依赖性的降低。SGLT2抑制剂没有诱导低血糖、严重低血糖、心血管疾病、骨折和全因死亡事件的风险,但是会增加不良反应、药物相关的不良反应、感染、糖尿病酮症酸中毒和肾脏疾病发生的概率,并且发生风险与剂量相关。 结论: 高剂量和中剂量SGLT2抑制剂在联合治疗的有效性方面有很好的成效,但可能引发不良反应,尤其是糖尿病酮症酸中毒。.

Keywords: 1型糖尿病; dosage; efficacy; safety; sodium glucose co-transporter 2 inhibitors; type 1 diabetes; 剂量; 安全性; 有效性; 葡萄糖协同转运体2抑制剂.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Therapy, Combination
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*

Substances

  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors