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Efficacy and safety of glucokinase activators for type 2 diabetes mellitus therapy: A meta-analysis of double-blind randomized controlled trials
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  • Yiqian Qu,
  • Keer Wang,
  • Shuyuan Lin,
  • Lingyong Cao,
  • Zhenghao Xu
Yiqian Qu
Zhejiang Chinese Medical University
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Keer Wang
Zhejiang Chinese Medical University
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Shuyuan Lin
Zhejiang Chinese Medical University
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Lingyong Cao
Zhejiang Chinese Medical University
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Zhenghao Xu
Zhejiang Chinese Medical University
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Abstract

Abstract Objectives: To assess the efficacy and safety of oral glucokinase activator (GKA) in the treatment of type 2 diabetes mellitus(T2DM). Methods: We searched PubMed, ClinicalTrails, Cochrane Library, Web of Science, and CNKI and collected randomized controlled trials (RCTs) of glucokinase activator in the treatment of T2DM. Revman5.3 software was used to do the meta-analysis. And the risk of bias in the included RCTs was evaluated according to the Cochrane tool. Results: Seven double-blind RTCs were included in the final analysis, with a total of 762 patients. Regarding the efficacy, GKAs significantly reduced fasting blood glucose (mean difference -0.71, 95% CI: -1.11 to -0.31, based on 459 patients from 5 literatures), and glycated hemoglobin also significantly reduced (mean difference: -0.65%, 95% CI: -0.82 to -0.48, based on 570 patients from 4 literatures). Regarding safety, GKAs did not affect the total rate of adverse events(AEs) (relative risk(RR) 1.11, 95% CI: 0.95 to 1.30, P = 0.19), but increased the risk of hypoglycemia (RR 1.81, 95% CI: 1.35 to 2.42, P < 0.0001). And the risk of diarrhea (RR 1.59, 95% CI: 0.7 to 3.65, P = 0.26), headache (RR 0.96, 95% CI: 0.41-2.21, P = 0.60) and nausea (RR 2.23, 95% CI: 0.55-9.12, P = 0.24) were not significantly increased in GKAs group. Conclusions: Oral GKAs combined with metformin has an obvious hypoglycemic effect on T2DM and good tolerance. Further clinical studies are still necessary to explore its long-term efficacy and safety. Keywords: Glucokinase; Glucokinase activator; Type 2 diabetes; Meta-analysis