Metformin is a commonly prescribed drug to treat Type 2 diabetes mellitus. It works by reducing glucose absorption from the intestines, by reducing the production of glucose by the liver and by improving sensitivity to insulin.
However, metformin is not completely effective in lowering blood glucose in all type 2 diabetes patients.
Why?
A group of researchers from Manipal Academy of Higher Education and Kasturba Medical College, Manipal, hypothesised that this is due to differences in gene expression in the two populations. So they started investigating the expression levels of genes involved in metformin response. A set of 22 such genes were shortlisted from the PharmGKB database.
The researchers then enrolled patients who had never been administered the drug before. They divided the patients into responders and non-responders based on whether their blood glucose level was lowered or not in response to metformin over a three-month study period.
The researchers collected RNA samples to study the genes expressed by the patients before metformin treatment. To understand the differences in the levels of gene expression between responders and non-responders, and to establish predictive biomarkers for metformin response, they used bioinformatics and R programming.
In responders, the gene, SLC22A4, involved in the transport and absorption of drugs in the intestine, was associated with improved response to metformin.
In non-responders, there was a reduction in the number of copies of the PPARGC1A gene – which may lead to altered glucose processing.
“A technique to detect the level of these critical genes will help doctors assess a patient’s predisposition to diabetes type 2 and to choose alternatives to metformin,” says Padmalatha Rai, Manipal Academy of Higher Education.
Journal of Endocrinological Investigation, (1720-8386, 2022);
DOI: 10.1007/s40618-022-01989-y
Reported By Karthic A
SIIPL, Pune
*This report was written during an online workshop organised by Current Science.
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COngratulation Karthik a well written story.
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