Endocrine Abstracts

Introduction: Individual variability in drug efficacy and safety due to genetic diversity is a major challenge for clinicians. Pharmacogenetics deals with inherited differences in the efficacy and safety responses to drugs. The incidence of type 2 diabetes (T2D) is increasing worldwide and the disease is reaching pandemic proportions. T2D is treated by oral and/or injectable drugs. The interindividual variability of T2D drug actions may be caused, at least in part, by genetic factors. This review outlines the contribution of pharmacogenomics to the efficacy outcome of glucagon-like peptide-1 receptor agonists (GLP1RAs) therapy in T2D.

Methods: A systematic search of literature was conducted using the search terms pharmacogenomics, type 2 diabetes, glucagon-like peptide-1 receptor agonists, and efficacy.

Results: Pharmacogenomics has identified the relevance of approximately 56 genes in the response to 7 pharmacological classes of antidiabetic drugs. More than 460 million people worldwide have T2D. According to the American Diabetes Association and the European Association for the Study of Diabetes, GLP1RAs are recommended as a second-line treatment in the management of T2D when there is a need for combination therapy. The identified genes influencing the efficacy outcome of GLP1RAs treatment [increased or decreased efficacy based on single nucleotide polymorphisms (SNPs)] include GLP1R (increased or decreased efficacy with rs6923761, rs3765467, rs10305420, and rs761386 SNPs), TCF7L2 (increased efficacy with rs7903146 SNP), CNR1 (increased efficacy with rs1049353 SNP), SORCS1 (increased efficacy with rs1416406 SNP), and WFS1 (decreased efficacy with rs10010131 SNP).

Conclusion: Pharmacogenomics is becoming an important tool in medicine. Education of clinicians is essential for the implementation of genetic testing into clinical practice. The use of genotype-guided dosing can help obtaining better efficacy and safety outcomes with drugs. Potential genomic markers for targeted GLP1RAs therapy have been identified. However, the number of studies is relatively limited and more comprehensive research including larger populations is needed to determine the therapeutic implication of incorporating precision medicine with the utilization of GLP1RAs in T2D.