Efficacy and safety of glucokinase activators for type 2 diabetes mellitus therapy: a meta-analysis of double-blind randomized controlled trials

Y. Qu, K. Wang, S. Lin, L. Cao, Z. Xu

College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. caolingyong@163.com

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• Metabolism

OBJECTIVE: We aimed to assess the efficacy and safety of oral glucokinase activator (GKA) in the treatment of type 2 diabetes mellitus (T2DM).

MATERIALS AND METHODS: We searched and collected randomized controlled trials (RCTs) of glucokinase activators in the treatment of T2DM from PubMed, ClinicalTrails, Cochrane Library, Web of Science, and CNKI databases. Revman5.3 software was used to do the meta-analysis, and the Cochrane tool was used to evaluate the risk of bias in the included RCTs.

RESULTS: Seven double-blind RTCs were included in the final analysis, with a total of 762 patients. For the efficacy, the meta-analysis found that GKAs lowed the levels of fasting blood glucose (FPG) (mean difference -0.71, 95% CI: -1.11 to -0.31, based on 459 patients from 5 works of literature) and glycated hemoglobin (HbA1c) (mean difference: -0.65%, 95% CI: -0.82 to -0.48, based on 570 patients from 4 works of literature). Subgroup analysis showed GKAs combined with metformin, but not used alone, reduced the levels of FPG. In terms of safety, GKAs did not affect the total rate of adverse events (AEs). GKAs did not affected the risks 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), but they increased the risk of hypoglycemia (RR 1.81, 95% CI: 1.35 to 2.42, p <0.0001, based on 570 patients from 4 literatures).

CONCLUSIONS: Oral GKAs combined with metformin has an evident hypoglycemic effect on T2DM, and they seem to be relatively good tolerant. Further clinical studies are still necessary to explore its long-term efficacy and safety.

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