Meta-analysis of Efficacy and Safety of SGLT- 2 Inhibitors Combined with Insulin for Type 1 Diabetes Mellitus / 中国药房

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.