Dorzagliatin is an oral medication for type 2 diabetes. It belongs to a novel class of drugs known as glucokinase activators (GKAs). These activators are sometimes referred to as “dual-acting glucokinase activators.” Dorzagliatin is specifically designed to address the underlying dysfunction in glucose regulation seen in type 2 diabetes.
How Dorzagliatin Works
Dorzagliatin’s mechanism of action centers on its interaction with glucokinase (GK), an enzyme that acts as a “glucose sensor” in the body. GK is expressed in various organs, including the pancreas, liver, and intestines. In pancreatic beta cells, GK activation is crucial for sensing glucose levels and triggering insulin release.
Dorzagliatin directly activates glucokinase, restoring its ability to properly sense glucose changes. This activation enhances glucose-stimulated insulin secretion from pancreatic beta cells. It also promotes the conversion of glucose into glycogen in the liver, which helps to reduce the liver’s glucose output. Dorzagliatin promotes insulin release in a glucose-dependent manner, meaning it primarily stimulates insulin when blood sugar levels are high. This glucose-dependent action helps reduce the risk of hypoglycemia, or dangerously low blood sugar, a concern with other insulin-stimulating medications.
Treating Type 2 Diabetes
Dorzagliatin helps regulate blood glucose levels in type 2 diabetes. It works by restoring glucose homeostasis, the body’s ability to maintain stable blood sugar. This includes controlling both fasting plasma glucose (FPG) and post-meal glucose (PPG) levels.
The medication can be used as a monotherapy for patients newly diagnosed with type 2 diabetes. It also serves as an add-on therapy for those whose blood glucose levels are not adequately controlled with other antidiabetic medications, such as metformin. Dorzagliatin’s ability to repair impaired glucose sensing aims to improve overall glycemic control.
Clinical Outcomes and Safety Profile
Clinical trials have shown dorzagliatin’s effectiveness in improving glycemic control in patients with type 2 diabetes. Studies, such as the SEED trial, demonstrated that dorzagliatin significantly reduced glycosylated hemoglobin (HbA1c) by approximately 1.07% as a monotherapy. When used as an add-on to metformin in the DAWN study, it reduced HbA1c by about 1.02%. These trials also observed reductions in both fasting and two-hour postprandial glucose levels.
Dorzagliatin has been well-tolerated. The incidence of adverse events in clinical trials has been similar to that of placebo. It has a low risk of severe hypoglycemia, with reported rates around 0.4% to 0.7% in studies. This is attributed to its glucose-dependent mechanism of action. While some studies noted a slight increase in body weight (around 0.38 kg) and BMI (around 0.14 kg/m2) compared to placebo, no drug-related serious adverse events were reported in combination therapy trials.
Current Development and Availability
Dorzagliatin was developed by Hua Medicine, a biotechnology company based in China. The drug received marketing approval from China’s National Medical Products Administration (NMPA) on September 30, 2022. This approval made it the first glucokinase activator launched globally for type 2 diabetes.
It is approved for use as a monotherapy in drug-naïve type 2 diabetes patients and in combination with metformin for those who are metformin-tolerant. Hua Medicine is collaborating with Bayer AG for the commercialization of dorzagliatin in China. The company also plans to explore its expansion into the Southeast Asia market and the United States, including preclinical studies for a second-generation dorzagliatin.