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Background Glucokinase activators (GKAs) are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus. Treatment with different GKAs has been shown to reduce blood glucose levels in these patients. We compared the efficacy/safety of GKAs in patients with type-2 diabetes mellitus through a meta-analysis. Methods We searched the PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. We computed the weighted mean difference (WMD) and 95% confidence interval (CI) for the change from baseline to the study endpoint for GKA versus placebo treatments. Results A total of 4 articles (5 studies) were included in the meta-analysis. GKAs were associated with reductions in glycated hemoglobin levels from baseline (WMD, -0.3%; 95% CI, -0.466% to -0.134%). No significant difference between GKA and placebo treatment was observed in the results of fasting plasma glucose levels from baseline (WMD 0.013 mmol/L; 95% CI, -0.304-0.33 mmol/L). A significantly higher change in 2-hour postprandial plasma glucose (2-h PPG) levels (WMD -2.434 mmol/L; 95% CI, -3.304 to -1.564 mmol/L) was observed following GKA than placebo treatment. GKAs were associated with a higher prevalence of causing hypoglycemic events than placebo treatment (risk difference [RD], 0.06; 95% CI 0.013-0.106). GKAs had no association with the risk of developing adverse effects (RD, 0.038; 95% CI, -0.03-0.106) and serious adverse events (RD, 0.01; 95% CI, -0.004-0.023). Conclusions GKAs were more effective for postprandial blood glucose control. However, these agents showed a significantly high risk of causing hypoglycemia. Prospero registration number CRD42021220364.

Background Glucokinase activators are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus (T2DM). Glucokinase activators blind to GK activate the enzyme allosterically. Treatment with different GKAs has been shown to reduce fasting and postprandial glucose in patients with type 2 diabetes. We compared the efficacy/safety of glucokinase activators in T2DM patients through a meta-analysis. Methods We searched PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. Two independent reviewers extracted the information from article. The quality of articles were assessed by 2 independent reviewers using the 5 items of scale proposed by Jadad. We computed the weighted mean difference and 95% confidence interval (CI) for a change from baseline to the study endpoint for glucokinase activators vs placebo. Egger test and Begg test were used to assess the possible publication bias caused by the tendency of published studies to be positive. Results The present meta-analysis will compare the efficacy and safety of glucokinase activators and placebo for the treatment of T2DM. Conclusions This meta-analysis will provide advanced evidence on the efficacy and safety of glucokinase activators for the treatment of T2DM. Ethics and dissemination Ethical approval and patient consent are not required because this study is a literature-based study. This systematic review and meta-analysis will be published in a peer-reviewed journal. Prospero registration number CRD42021220364.