Pharmacogenetics of incretin-based therapies

Interindividual variability in the efficacy of various glucose-lowering drugs has been previously reported and partly explained by genetic variants. The aim of this review was to summarize currently available information on pharmacogenetic studies of the efficacy of incretin-based therapies such as glucagon-like peptide 1 (GLP-1) receptor agonists (GLP1RA) and dipeptidyl peptidase 4 (DPP-4i) inhibitors. Several missense variants of the GLP1R gene have been associated with the effects of GLP1RA or DPP-4 inhibitors on glycaemic compensation or weight. Pharmacogenetic effects have also been reported for several type 2 diabetes-associated loci, such as TCF7L2, THADA, MTNR1B, CDKAL1, KCNQ1, KCNJ11, and PAM in candidate gene approach studies. Genome-wide pharmacogenetic studies have identified new genes with potentially relevant pharmacogenetic effects (CTRB1/2, ARRB1, PRKD1). Although none of these genetic associations are currently used in guiding the treatment choices in clinical practice, they offer valuable insights bringing us a little closer to precision medicine.