Genetic Variants Could Predict Drug Safety

Testing a genetic variant for a proposed drug could predict safety profile.

A recent study found that a genetic approach could identify potential adverse events before the drug is made.

This approach involves finding genetic variants that mimic the drug on its target and checks if these variants can cause other conditions in patients, according to the study published by Science Translational Medicine.

The FDA requires that anti-diabetic medication cannot have any cardiovascular adverse effects, but sometimes safety profiles are not clear until late in the development process after millions of dollars have been spent.

According to the study, glucose-lowering glucagon-like peptide-1 receptor (GLP1R) antagonists bind to the GLP-1 receptor to increase insulin production and reduces blood sugar. However, the cardiovascular safety of this class of drugs is unknown.

Researchers analyzed variations of DNA-encoding drug targets for type 2 diabetes and obesity in approximately 12,000 patients. Researchers were able to identify a variation of the GLP1R gene that was seen to decrease fasting glucose, as well as decreasing the risk of type 2 diabetes.

This variant appeared to mimic the drug and researchers were able to confirm their finding in 40,000 additional patients, according to the study.

Genetic data was analyzed, which showed the same variant can decrease the risk of heart disease.

"This further suggests that human genetics can support the development of new therapies, and can offer insights into their safety profile early in the development process," said the study’s first author Dr Robert Scott.

Clinical trials evaluating the cardiovascular safety of GLP1R-antagonists are currently underway.

"Researching and developing new medicines is a lengthy, expensive and risky journey, and any insights we can gain in to the processes of the body related to disease could help improve our ability to succeed," concluded joint senior author Dawn Waterworth, PhD.