埃格列净单药治疗2型糖尿病安全性的Meta分析

Safety of Ertugliflozin as a Monotherapy for the Treatment of Type Ⅱ Diabetes: a Meta-Analysis

目的系统评价埃格列净单药治疗2型糖尿病(T2DM)的安全性。方法计算机检索中国知网、万方、PubMed、The Cochrane Library、Embase、Clinical Trials数据库中有关埃格列净治疗T2DM的RCT研究,随后根据纳入与排除标准筛选文献,提取文献资料,并用Cochrane评价手册5.3.3评价文献质量,最后采用RevMan5.3软件和Stata14.0软件进行Meta分析。结果最终纳入6篇RCT研究,累计4 078例患者。Meta分析结果显示,治疗26周,本品发生生殖器真菌感染(GMI)风险显著高于对照组(RR=6.25,95%CI:3.13~12.48,P<0.000 01),女性发生GMI的风险高于男性(RR=2.28,95%CI:1.55~3.36,P<0.000 1);52周时,本品发生GMI风险显著高于对照组(RR=4.44,95%CI:2.98~6.61,P<0.000 01),15 mg剂量亚组,女性发生GMI的风险高于男性(RR=2.89,95%CI:1.67~5.00,P=0.000 2)。治疗52周时,与对照组相比,在泌尿道感染、低容量血症、低血糖症状、估计肾小球滤过率(ΔeGFR)及ΔeGFR(>30%)患者人数方面,发生风险均无显著性差异;5和15 mg剂量组间相比较,上述6个安全性指标的发生风险无显著性差异。结论埃格列净易引发生殖器真菌感染,且女性发生风险高于男性,同时也易使eGFR降低,但多为可逆性,不易引起泌尿道感染、低容量血症和低血糖;剂量未见对埃格列净安全性有明显影响。

OBJECTIVE To systematically evaluate the safety of ertugliflozin as a monotherapy for the treatment of type Ⅱ diabetes. METHODS The randomized controlled trials(RCTs) of ertugliflozin for type Ⅱ diabetes were searched in the clinical trial registries and the related databases, such as CNKI, WANFANG, The Cochrane Library, Embase and Clinical Trials. The literatures were screened according to inclusion and exclusion criterias.After the data extraction and assessing the quality of included studies with Cochrane Handbook 5.3.3, Meta-analysis was conducted with RevMan5.3 software and the sensitivity of outcomes were analyzed by the Stata14.0. RESULTS The six individual randomized controlled trials were eligible. The 4 078 patients were enrolled. There are some results of Meta-analysis. At 26 weeks, compared to the control subjects, the risk of genital mycotic infection(GMI) in ertugliflozin group was higher(RR=6.25, 95%CI: 2.98-6.61, P<0.000 01).The risk of female patients with GMI was higher compared to that of male (RR=2.28,95%CI:1.55-3.36,P<0.000 1). At 52 weeks, compared to the control subjects, the risk of GMI in ertugliflozin group was higher (RR=4.44, 95% CI: 2.98-6.61, P<0.000 01). The risk of female patients with GMI was higher compared to that of male patients in the subgroup 15 mg ( RR=2.89, 95% CI:1.67-5.00, P=0.000 2). At 52 weeks,compared to the control group, the risk of urinary tract infection, symptomatic hypoglycaemia, hypovolaemia, estimated glomerular filtration(ΔeGFR)and the number of patients who sede crease from baseline >30% in eGFR were no significant difference. There were no significant difference between 5 and 15 mg group on the safety indicators at 52 weeks. CONCLUSION Ertugliflozin could cause GMI regularly. And the risk of female patients with GMI was higher than male. Meanwhile, it was easy to reduce eGFR, but most of them were reversible.Ertugliflozin was safe in urinary tract infection, symptomatic hypoglycaemia and hypovolaemia. However, there is no obvious difference in the safety of different dosage groups.