Efficacy and safety of novel dual glucokinase activator dorzagliatin in type-2 diabetes A meta-analysis

Abstract

Background & aimsGlucokinase has a critical role in regulating glucose homeostasis in humans, and has been a target for diabetes drug development since 1990s. Dorzagliatin is a novel allosteric dual glucokinase activator targeting both pancreatic and hepatic glucokinase. No meta-analysis has analysed the efficacy and safety of dorzagliatin in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap. MethodsElectronic databases were searched for RCTs involving T2DM patients receiving dorzagliatin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood glucose parameters, lipids, insulin-resistance and adverse events. ResultsFrom initially screened 17 articles, data from 3 RCTs (1333 patients) was analysed. Over 12–24 weeks use, dorzagliatin had significantly higher lowering of HbA1c [MD -0.66% (95%CI: −0.74 to −0.59); P < 0.01; I2 = 99%], fasting glucose [MD -32.03 mg/dl (95%CI: 45.12 to −18.94); P < 0.01; I2 = 100%], 2-h post-prandial glucose [MD -43.49 mg/dl (95%CI: −46.26 to −40.72); P < 0.01; I2 = 90%] along with greater number of patients achieving HbA1c<7% [OR 6.01 (95% CI: 2.50–14.46); P < 0.01; I2 = 83%], as compared to placebo. Dorzagliatin was associated with significant elevation of triglycerides [MD 0.43 mmol/L (95%CI:0.30–0.56); P < 0.01; I2 = 0%], greater occurrence of hyperlipidaemia [RR 1.52 (95% CI:1.05–2.18); P = 0.03; I2 = 0%], and increase in body-weight [MD 0.40 kg (95%CI:0.06–0.75); P = 0.03; I2 = 0%], compared to placebo. The occurrence of total-adverse-events [RR 1.43 (95%CI:1.11–1.83); P < 0.01; I2 = 0%] but not severe adverse-events [RR 0.92 (95%CI:0.54–1.57); P = 0.76; I2 = 0%] was significantly higher with dorzagliatin. ConclusionDorzagliatin has good glycaemic efficacy and well tolerated over 6-months use. Mild increase in body-weight, serum triglycerides and overall adverse events remain issues of concern warranting further evaluation in longer clinical trials with active controls.