葡萄糖激酶激活剂治疗2型糖尿病有效性和安全性的Meta分析

Efficacy and safety of glucokinase activators for type 2 diabetes mellitus therapy: a meta-analysis

目的 系统评价葡萄糖激酶激活剂治疗2型糖尿病的有效性和安全性。方法 检索PubMed、Cochrane Library、Web of Science、Embase、中国知网等数据库,时间为建库至2022年3月。纳入葡萄糖激酶激活剂与安慰剂(或其他口服降糖药)对照治疗2型糖尿病的随机对照试验,提取资料并用RevMan 5.4软件进行Meta分析。结果 纳入9项研究,2 150名患者。降糖效果方面,与对照组相比,葡萄糖激酶激活剂能显著降低糖尿病患者糖化血红蛋白[MD=-0.40,95%CI(-0.53,-0.26),P<0.000 01]、空腹血糖[MD=-0.53,95%CI(-0.85,-0.20),P=0.001]和餐后2 h血糖[MD=-2.28,95%CI(-2.68,-1.88),P<0.000 01]。安全性方面,总体上葡萄糖激酶激活剂的低血糖发生率要高于对照组[RR=1.55,95%CI(1.20,2.01),P=0.000 8];根据葡萄糖激酶激活剂激活的脏器进行亚组分析,胰腺肝脏双激活剂组[RR=1.44,95%CI(1.11,1.89),P=0.007]和肝脏选择性激活剂组[RR=2.26,95%CI(1.02,5.03),P=0.05]的低血糖发生率均要高于对照组,差异有统计学意义。结论 葡萄糖激酶激活剂能有效降低2型糖尿病患者的糖化血红蛋白、空腹血糖及餐后2 h血糖,但其低血糖风险仍有待解决。

OBJECTIVE To systematically evaluate the efficacy and safety of glucokinase activators in the treatment of type 2diabetes mellitus. METHODS PubMed, Cochrane Library, Web of Science, Embase and CNKI databases were searched from the inception to March 2022. Randomized controlled trials about glucokinase activators versus placebo(or other oral hypoglycemic agents) in the treatment of type 2 diabetes were included, data were extracted and meta-analysis was analyzed using RevMan 5.4 software. RESULTS A total of 9 studies with 215 0 patients were included. In terms of hypoglycemic effect, compared with control group, glucokinase activators significantly reduced glycosylated hemoglobin(HbA1c) [MD=-0.40, 95%CI(-0.53,-0.26), P<0.000 01], fasting blood glucose[MD=-0.53, 95%CI(-0.85,-0.20), P=0.001] and 2 h postprandial blood glucose [MD=-2.28, 95%CI(-2.68,-1.88), P<0.000 01] in diabetic patients. In terms of safety, the incidence of hypoglycemia caused by glucokinase activators was higher than control group on the whole [RR=1.55, 95%CI(1.20,2.01), P=0.000 8]. According to the subgroup analysis of organs activated by glucokinase activator, the incidence of hypoglycemia in the pancreas-liver dual activator group [RR=1.44, 95%CI(1.11,1.89), P=0.007] and liver-selective activator group [RR=2.26, 95%CI(1.02,5.03), P=0.05] was higher than that in the control group, the difference was statistically significant.CONCLUSIONS Glucokinase activators can effectively reduce HbA1c, fasting blood glucose and 2 h postprandial blood glucose in patients with type 2 diabetes, but the risk of hypoglycemia remains to be addressed.