Advancements in SGLT2 inhibitors: pharmacokinetics, pharmacodynamics, and clinical efficacy with a focus on pharmacogenomics

Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a pivotal advancement in the treatment of type 2 diabetes mellitus (T2DM), offering substantial improvements in glycemic control, cardiovascular protection, and renal outcomes. This review explores the pharmacokinetics, pharmacodynamics, and clinical efficacy of SGLT2 inhibitors, with a particular focus on pharmacogenomics and its impact on individual patient response. Bexagliflozin, a potent SGLT2 inhibitor, exhibits robust glycemic control through selective SGLT2 inhibition, while studies on luseogliflozin, ertugliflozin, tofogliflozin, and remogliflozin have further demonstrated the versatility and safety of this drug class. These inhibitors not only reduce HbA1c but also lower blood pressure, improve renal outcomes, and reduce the risk of major adverse cardiovascular events. Pharmacogenomics has revealed genetic polymorphisms that affect the metabolism and efficacy of SGLT2 inhibitors, guiding more precise therapeutic decisions. Variants in genes like SLC5A2 and CYP enzymes influence drug transport, metabolism, and response, paving the way for personalized treatment approaches. This growing understanding underscores the potential for pharmacogenomics to refine the selection of SGLT2 inhibitors for optimal efficacy and minimal side effects. Despite promising results, further research is needed to fully integrate pharmacogenomics into clinical practice. As personalized medicine continues to evolve, SGLT2 inhibitors, bolstered by pharmacogenomic insights, offer a compelling avenue for enhancing the management of T2DM, ultimately transforming patient care with a more tailored and effective approach.