Dorzagliatin novel hypoglycemic agent for effective management of type 2 diabetes

A mild increase in total cholesterol (TC) and triglyceride (TG) was seen with dorzagliatin. Still, it did not increase hyperlipidemia incidence, and the slight increase in BMI and body weight was not clinically relevant. No drug-related adverse events (AEs) were reported at a higher incidence than placebo alone. Serious adverse events of dorzagliatin, such as hypoglycemia and hyperlipidemia, were comparable to that of a placebo, and dorzagliatin demonstrated a good safety profile.

Dorzagliatin is a novel hypoglycemic agent for treating T2DM with dual agonistic effects on glucokinase (GK) in the liver and pancreas. It can promote insulin secretion and hepatic glycogen production, improve glucose utilization by peripheral tissue, and improve the function of β-cells in T2DM patients. In patients with type 2 diabetes, dorzagliatin has been reported to significantly and consistently reduce HbA1c (glycated hemoglobin A1c) and is well-tolerated. Currently, there is no meta-analysis related to dorzagliatin, and evidence-based evidence of dorzagliatin for T2DM remains to be explained.

Against the above background, Yunfeng Yu from the Hunan University of Chinese Medicine in Changsha, China, and colleagues aimed to evaluate the safety and efficacy of dorzagliatin in treating type 2 diabetes by using trial sequential analysis (TSA) and meta-analysis.

For this purpose, the researchers searched for clinical trials of dorzagliatin for type 2 diabetes in eight databases, with a time limit of July 2022. They carried out included studies that met the requirements for TSA and meta-analysis.

The authors reported the following findings:

• In terms of efficacy endpoints, a meta-analysis revealed that dorzagliatin decreased HbA1c [mean difference (MD) −0.65%], fasting plasma glucose (FPG) (MD −9.22 mg/dL), two h postprandial glucose (2h-PPG) (MD −48.70 mg/dL), homeostasis model assessment 2 of insulin resistance (HOMA2-IR) (MD −0.07) and increased homeostasis model assessment 2 of ß-cells function (HOMA2-β) (MD 2.69) compared with placebo.
• TSA revealed that except for HOMA2-IR, the benefits seen for the current information set were conclusive.
• Dorzagliatin, in comparison to the placebo, increased triglyceride(TG) (MD 0.43 mmol/L), total cholesterol (TC) (MD 0.13 mmol/L), body weight (MD 0.38 kg) and body mass index (BMI) (MD 0.14 kg/m2), while low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and diastolic blood pressure (DBP) were comparable.
• TSA showed that TC, TG, BMI, and body weight were conclusive.
• Regarding safety endpoints, dorzagliatin increased total adverse events [risk ratio (RR) 1.56], while serious AEs, hyperlipidemia, and hypoglycaemia was all comparable.
• TSA indicated that the findings need to be confirmed by additional studies. Harbord regression showed no publication bias.

"Current clinical trials have been conducted with dorzagliatin alone or in combination with metformin, and the role of dorzagliatin in other combinations needs further exploration," the authors concluded.

Reference:

Yu Y, Yang X, Tong K, Yin S, Hu G, Zhang F, Jiang P, Zhou M and Jian W (2022) Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis. Front. Cardiovasc. Med. 9:1041044. doi: 10.3389/fcvm.2022.1041044