9 August 2016
Genetic differences between patients could account for why the effectiveness of the widely used type 2 diabetes drug metformin can differ between patients.
The study (published in Nature Genetics this week) the largest of its kind so far, was conducted by the international Metformin genetics consortium, led by researchers from the University of Dundee and the University of California, San Francisco. The team conducted a genome wide association study on a multi-ethnic cohort of over 13,000 patients to investigate whether genome variation could account for why responses to the drug metformin differ from person to person.
The GWAS identified that a variation within the gene SLC2A2 correlated with variation in response to the drug. The gene encodes the protein GLUT2, which regulates movement of glucose between the liver, blood and kidneys. The new discovery might offer a biologically plausible explanation for variations in efficacy of the drug between patients. Intriguingly, the team also found that the effect of the variation in the SLCA2 gene was greater in obese patients and that in obese patients carrying two copies of the gene variant the improved effectiveness of the drug amounted to the equivalent of an extra 550mg dose of the drug.
Professor Pearson, one of two lead authors said that it was an ‘exciting discovery that demonstrates how a patient’s genetics can determine how well, or poorly, a drug works.’
Although this study does not provide the direct clinical evidence that would be needed to demonstrate that this genetic marker could be used to personalise metformin use, it certainly highlights the need to consider how genomic variation in different populations affects response not only to newly developed ‘stratified medicines’ but also to the enormous number of existing medications already in use today.
Our own Leila Luheshi, Head of Science at the PHG Foundation had this to stay about the newly published study:
‘A future health system aiming to deliver more personalised healthcare will need to replicate this type of exploratory study systematically across a range of conditions to have true population health impact. Achieving this will require the collection and utilisation of whole-population health record data that capture the full range of drugs and other interventions, in combination with the characteristics - such as genome sequence, other biomarkers and environmental factors - of the people to whom they are applied. The aim of such studies should be to identify new biomarker-disease relationships like these that are worthy of following up in more carefully controlled trials to test the clinical impact of potential stratification or personalisation of care.’