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Genomics indicates likelihood of side effects in diabetes drug hunt

20 June 2016
Appeared in BioNews 856

Genomics could help predict drug side effects in patients with type 2 diabetes early in the drug development process, according to a study.

The proof-of-principle study suggests that genetic data could be used to narrow down the search for drugs that are safe as well as effective.

Type 2 diabetes poses a high cardiovascular risk to patients, so the US Food and Drug Administration has recommended that pharmaceuticals must not only demonstrate clinical efficacy, but must also not increase patients' cardiovascular risk.  

This is a challenge, according to Dr Francis Collins, director of the US National Institutes of Health. 'Long-term health risks may not become clear until thousands or even tens of thousands of people have received [a drug] over the course of many years,' he wrote in a blog.

Writing in the journal Science Translational Medicine, researchers from the University of Cambridge and GlaxoSmithKline say they used data from 50,000 people to identify six genes that influence type 2 diabetes and obesity, showing promise as potential drug targets.

One particular variant of the GLP1R gene was associated with a lower fasting glucose level and reduced type 2 diabetes risk. Analysis indicated that the variant mimics the effects of a class of antidiabetic drugs called (GLP1R)-agonists. These drugs bind to the GLP-1 receptor to increase insulin production, helping reduce levels of blood sugar. The results were confirmed in another 40,000 individuals.

The researchers then assessed whether the variant influenced cardiovascular risk using data from over 60,000 people with coronary heart disease and 163,000 controls. They found that the variant actually gives protection against heart disease, which gives them confidence that (GLP1R)-agonists would not increase cardiovascular risk and might even lower it.

'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 Dr Robert Scott from the Medical Research Council Epidemiology Unit at the University of Cambridge, the study's first author.

'Researching and developing new medicines is a lengthy, expensive and risky journey, and any insights we can gain into the processes of the body related to disease could help improve our ability to succeed,' said Dr Dawn Waterworth, joint senior author from GlaxoSmithKline.

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