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