Glucokinase Activators Outperform Placebo in Patients With Type 2 Diabetes

Glucokinase activators (GKAs) were more effective than placebo for postprandial blood glucose control in patients with type 2 diabetes, but they also showed a comparably high risk of causing hypoglycemia. Researchers published their findings online in the journal Medicine.

“GKAs are a relatively new therapeutic class of oral anti-hyperglycemic agents for managing type 2 diabetes mellitus,” researchers wrote. “In order to provide new medical evidence for clinical treatment, it is necessary to study the efficacy and safety of GKAs in the management of this disease."

Researchers conducted a systematic review and meta-analysis of five double-blind randomized controlled trials to compare the effects of GKAs with placebo.

The meta-analysis revealed a significantly higher change in 2-hour postprandial plasma glucose levels with GKAs compared with placebo (the weighted mean difference was -2.434  mmol/L). However, GKAs did not have a significantly greater effect than placebo on fasting blood glucose levels, with a weighted mean difference of 0.013  mmol/L.

GKAs were associated with significant reductions in glycated hemoglobin levels from baseline (the weighted mean difference was -0.3%). Researchers speculated the reduction was the result of the change in postprandial blood glucose levels.

The risk of adverse effects and serious adverse events with GKAs were low. The study did find an increased prevalence of hypoglycemic events with GKAs compared with placebo (the risk difference was 0.06).

“Nonetheless, GKAs could be an attractive choice for the treatment of type 2 diabetes mellitus,” advised researchers, who called for continued evaluation of the new hypoglycemic agents to determine efficacy and safety over the long term.

Reference:
Gao Q, Zhang W, Li T, Yang G, Zhu W, Chen N, Jin H. The efficacy and safety of glucokinase activators for the treatment of type-2 diabetes mellitus: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021;100(40):e27476. doi:10.1097/MD.0000000000024873