Pharmacogenetics of new classes of antidiabetic drugs

Abstract

Type 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D.

The association between previous use of anti‐obesity medication and semaglutide weight loss outcomes

“…24 Additionally, a decreased response could be explained by patients' genetic profile, as studies have found a significant association between specific single nucleotide polymporphisms, liraglutide treatment and outcomes in terms of gastric emptying, BMI and fat mass. 25 Thus, one would assume that if an individual had a suboptimal response to a certain drug, then their response to another drug within the same class would be comparable. It might be more beneficial to switch these individuals to another drug class for improved results.…”

“…It is likely that patients with a slower gastric emptying at baseline might not benefit as much from the effect of GLP‐1 receptor agonists on gastric motility and might have a higher propensity towards developing side effects, making them less adherent to the medication 24 . Additionally, a decreased response could be explained by patients' genetic profile, as studies have found a significant association between specific single nucleotide polymporphisms, liraglutide treatment and outcomes in terms of gastric emptying, BMI and fat mass 25 …”

Clinical effectiveness and pharmacokinetics of gliflozin from the point of view of individual genetic characteristics: A review

“…Ингибиторы натрий-глюкозного котранспортера 2-го типа (sodium-glucose transport proteins 2 inhibitors -SGLT2i) являются дополнением к пероральным антидиабетическим препаратам, назначаемым врачами во всем мире в качестве средств второго ряда [1]. Однако в последних опубликованных российских клинических рекомендациях по лечению сахарного диабета 2-го типа (СД 2) у взрослых применение SGLT2i приоритетно при хронической сердечной недостаточности и хронической болезни почек.…”