The effects and safety of activators of glucokinase versus placebo in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

We undertook a systematic review and meta-analysis to assess the effects and safety of activators of glucokinase (GKAs) in patients with type 2 diabetes mellitus (T2DM). 11 RCTs, including 2,429 participants, are enrolled in our study. According to different doses, we divided the studies into 3 groups: low-dose group, medium-dose group and high-dose group for subgroup analysis. There were decreases of HbA1c in all dose group (WMD = -0.27, 95%CI (-0.51~ -0.03), Z = 2.17, p = 0.03; WMD = -0.37, 95%CI (-0.58~ -0.16), Z = 3.41, p = 0.0006; WMD = -0.60, 95%CI (-0.86~ -0.33), Z = 4.43, p < 0.00001). Though the total risk of hypoglycemia is absolutely low, in the high-dose group higher hypoglycemia than the placebo can be observed (RR = 0.03, 95%CI (0.00~0.06), Z = 2.27, p = 0.02). In addition, the study found that the drug was less likely to have adverse reactions such as diarrhea, headache and dizziness, nasopharyngitis and upper respiratory tract infection (RR = 0.76, 95%CI (0.36~1.60), Z = 0.73, p = 0.47; RR = 1.26, 95%CI (0.73~2.17), Z = 0.83, p = 0.41; RR = 0.71, 95%CI (0.41~1.22), Z = 1.25, p = 0.21; RR = 1.61, 95%CI (0.77~3.36), Z = 1.26, p = 0.21). It concludes that GKAs are relatively effective and safe in the treatment of patients with T2DM, but in consideration of the potential risk of hypoglycemia in the high-dose group, the low-dose and medium-dose group, in the clinical practice, can be an excellent choice.

Keywords: Activators of glucokinase; Meta-analysis; Type 2 diabetes mellitus.