A Summary: Pharmacogenomics of Drug Response in Type 2 Diabetes: Toward the Definition of Tailored

Therapies?

Diabetes is a detrimental disease with proliferating occurrence. Not only does it interfere with our
glucose levels but also affects other systems such as the cardiovascular and nervous systems. Its perilous
nature have started a chain reaction in clinical studies regarding the disease in light of finding the
ameliorating solution. Currently, there are three drugs that are more widely used namely, sulphonylureas,
metformin and thiazolidinediones. This article is a scientific journal review article, hence the complete
methodology for the respective studies were not in-detail. Starting with sulphonylurea, studies conclude that
differences or polymorphisms in the coding-gene affect the response given by our body to the drug taken.
Specifically, an example would be the comparison between TT and GG genotypes of an rs12255372 allelic
variance of the gene TCF7L2. It has been revealed in a study that early sulphonylurea(SUs) treatment in
those with TT genotypes showed a higher probability to fail than their GG genotype counter parts; similarly,
another study showed a lower reduction of HbA1c levels in those TT genotypes compared to CC
homozygous genotypes. This study on SU association with polymorphism was done by using DARTS/
MEMO database on type 2 Diabetes patients for classification while a 3-12 month frame of medication was
initiated to observe the response. Moving to metformin, Zhou et al. demonstrated that nucleotide variations
in genes involved in DNA repair and cell cycle control determine altered response to metformin, in terms of
glycemic response and considering HbA1c < 7% as treatment achievement. Focusing on the gene SLC22A1,
the 420del polymorphism showed a more significant decrease in glucose plasma levels than the other
variances. R61c polymorphism on the other hand showed a reduced expression of OCT1 protein, which
could affect transport. The study on 420del carriers was a 2x2x2 factorial, prospective, randomized, double-
blind, placebo-controlled, multicentre study which involved 159 patients who received 2 grams of metformin
daily. Measurements were obtained after 3, 6 and 9 months of treatment. Lastly, on the drug
thiazolidinediones, there has yet to be a definite conclusion regarding its efficacy as various studies showed
conflicting results. This inconclusiveness leads us to more specific studies such as the use of New-
Generation Sequencing (NGS) in studies to show more about the association of polymorphism and drug
response. The researchers hope, in respect with the shift to NGS, that genetic variants will be identified and
the phenomena of drug alteration due to polymorphism be concluded. This review article clearly
foreshadows personalized treatment as more studies continue to associate nucleotide polymorphism to
altered drug response. The studies mentioned in this article awakens every medical practitioner to the
severity of a nomothetic approach towards medication.