The efficacy and safety of glucokinase activators for the treatment of type-2 diabetes mellitus: A meta-analysis

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.