In a nutshell
This study assessed the effectiveness and safety of adding dorzagliatin (HMS552) to metformin therapy in patients with type 2 diabetes (T2D) with inadequately controlled blood glucose (sugar) while using metformin (Glucophage) alone. The data showed effective blood glucose control, good tolerance, and safety in patients treated with dorzagliatin and metformin.
Metformin is commonly the first-line medication used in the treatment of T2D. It is used with diet and exercise, and sometimes with other anti-diabetic drugs. Metformin controls blood glucose by lowering its liver production, decreasing absorption in the intestine, and improving uptake and utilization by increasing insulin sensitivity. However, as the function of beta cells (the pancreatic cells that make insulin) progressively declines, metformin is less effective on its own.
Glucokinase (GK) is an enzyme that monitors and regulates glucose levels. It does this through its effect on glucose-stimulated insulin secretion (GSIS), glucagon, and glucagon-like peptide-1 (GLP-1). It also influences glucose uptake by the liver. If GK activity decreases, blood glucose increases. GK activators (GKAs) are medications that enhance GK activity. Dorzagliatin is an orally-administered, full-GKA that has effects on GK in the liver and pancreas. There is a need to investigate the potential benefits of adding dorzagliatin to metformin therapy in patients with T2D that have inadequately controlled blood glucose.
Methods & findings
This study included 767 patients with T2D. Patients were randomly assigned to receive either dorzagliatin or a placebo as an add-on to metformin treatment. 382 patients received 75 mg of dorzagliatin twice daily with 1500 mg of metformin (group 1). 385 patients received a twice-daily placebo with 1500 mg of metformin (group 2). After 24 weeks, all patients switched to 75 mg of dorzagliatin twice daily with 1500 mg of daily metformin. The study lasted for 1 year.
Patients given dorzagliatin and metformin showed a reduction in HbA1c (blood glucose control over the last 2-3 months) of -1.02% compared to baseline at 24 weeks. Those that received a placebo and metformin had a reduction of -0.36% in HbA1c from baseline at 24 weeks.
After 24 weeks, 44.4% of patients in group 1 achieved an HbA1c level below 7% compared to 10.7% in group 2.
There were no significant differences in severity and type of side effects between treatment groups. Low blood glucose levels (hypoglycemia) occurred in 0.8% of patients in the dorzagliatin and metformin treatment group at 24 weeks.
The bottom line
The study indicated that dorzagliatin added to metformin had good tolerance and safety, and improved blood glucose control in patients with inadequately controlled T2D.
The fine print
The study was conducted on patients from China only. Further studies are required using additional anti-diabetic drug combinations in genetically diverse populations. This study was funded by Hua Medicine, the manufacturer of dorzagliatin.
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Original Title :
Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.