Public Release: 

Cheering on a potential diabetes drug from bench to bedside

American Association for the Advancement of Science

Scientists have developed a promising compound that targets a protein well-known to be implicated in type 2 diabetes, which - unlike different versions of its kind currently under investigation - proved to be safe and effective in a phase 2 clinical trial of 190 type 2 diabetes patients. The drug, dubbed TTP399, was initially evaluated by the researchers in rats, mice and minipigs with success, and hints that TTP399 may someday pave the way to better treatment options for the condition. According to the Centers for Disease Control and Prevention, over 100 million adults in the U.S. have diabetes or prediabetes, representing a growing need for new therapies that do not lead to adverse events or loss of efficacy over time. Glucokinase (GK) is a protein involved in the breakdown of sugar and has been previously identified as a type 2 diabetes therapeutic target. While multiple small-molecule activators of GK are in clinical development, their potential is hampered by side effects such as low blood sugar (or hypoglycemia) and elevated triglyceride concentrations (which can be harmful to the heart). Here, Adrian Vella and colleagues administered TTP399 to rodent models of type 2 diabetes and observed an improvement in blood sugar levels (or glycemic control), as well as decreased amounts of liver fat. To validate these findings, they conducted a six-month phase 2 clinical trial assessing TTP399 in 190 participants with type 2 diabetes. Importantly, TTP399 did not cause hypoglycemia, had no detrimental effect on plasma lipids or liver enzymes, and did not increase blood pressure. The authors say that additional studies and larger clinical trials are required to determine if efficacy can be sustained beyond six months.

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