Pharmacogenomics of glibenclamide in patients with type 2 diabetes mellitus: A systematic review

Introduction: One of the most widely used anti-diabetic drugs is sulfonylureas, which is often used as one of the first-line drugs in the treatment of type 2 diabetes. Due to the effect of the patient's genetic structure on the drug response (personalized medicine), the identification of genetic variations not only reduces the rate of adverse drug reactions but can also predict the effectiveness of drugs. This study aimed to systematically review the pharmacogenomics of glibenclamide in type 2 diabetes. Materials and Methods: This systematic review was performed based on PRISMA flowchart. Using the search terms including "variant", “sulfonylurea”, "glibenclamide", "diabetes mellitus", "SNP" or their equivalents, a comprehensive search of the PubMed, Scopus and Web of Science databases was conducted until January 1, 2021. An initial search yielded 125 articles. Results: Finally, in nine articles included in this systematic review, glibenclamide monotherapy was performed in 3032 patients. Most studies were conducted in China and the most common methods of genotyping were RFLP-PCR and direct sequencing. The most common genes studied were CYP2C9, KCNJ11 and TCF7L2. The results of studies showed a significant effect of CYP2C9 polymorphism on appropriate therapeutic response and KCNJ11 gene polymorphism on failure of glibenclamide treatment. Conclusion: Among all genetic factors and specific genotypes of proteins involved in the metabolism of glibenclamide, CYP2C9 gene polymorphism has a role in proper response to treatment and KCNJ11 gene polymorphism has a role in treatment failure and hypoglycemic effects of glibenclamide.