Diabetes

Diabetes Mellitus can be treated with nine different classes of drugs, many of which are metabolized by pharmacogenetics proteins (4). Sulfonylureas (SU) drugs for example, are among the most commonly prescribed hypoglycemic agents today, yet up to 20% of patients do not achieve sufficient glycemic levels even at high doses. Another 10% of patients that initially respond to SU medications will lose the ability to maintain normal glucose levels. These statistics are not random, they reflect CYP2C9 genotype prevalence (4). Patients who possess variant CYP2C9 genotypes can require dosage adjustments for these medications of up to 80% (3). New diabetes drugs are increasingly displaying pharmacogenetics language on their FDA labels, and additional genes are currently being studied to improve the efficacy of diabetes medications.

Diabetes Relevant Genes In The PRIMER Panel

Gene - Gene Product Description 

CYP2C19 – Metabolizes approximately 10-15% of all drugs, including clopidogrel, citalopram, diazepam, and many of the proton pump inhibitors.  Detecting variants of the CYP2C19 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP2C19 substrates.

CYP2C9 – Metabolizes approximately 10% of all drugs, including warfarin, phenytoin, non-steroidal anti-inflammatory drugs (NSAIDs), and antihyperglycemic sulphonylureas.  Detecting variants of the CYP2C9 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP2C9 substrates.

SLCO1B1 – This gene encodes the liver enzyme OATP1B1, which assists in transport of statins medications into the liver. Roughly 15% of the population possess the *5 variant, an inherited form of SLOC1B1 which increases risk of statin-induced myopathy 3 to 5 fold. Risk of myopathy with the *5 variant is most closely associated with simvastatin and to a lesser extent, atorvastatin. Patients with the *5 variant may need the lowest doses of simvastatin or an alternative statin to reduce risk of myopathy. 

References 

1) Menu of Tests [Internet]Louisville, KY: PGXL Laboratories; c2016 [cited 2016 11/20]. Available from: http://www.pgxlab.com/test-menu/.

2) Pathways for common medications. Louisville, KY: PGXL Laboratories; 2016:PGXL Primer. Personalized Medicine. Results For Life.

3) Semiz S, Dujic T, Causevic A. Pharmacogenetics and personalized treatment of type 2 diabetes. Biochemia Medica 2013 11;23(2):154-71.

4) Topic E. The role of pharmacogenetics in the treatment of diabetes mellitus. Journal of Medical Biochemistry 2014 01;33(1):58-70.

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