Identification of clinical and pharmacogenetic factors influencing metformin response in Type 2 diabetes mellitus

Pharmacogenomics. 2023 Aug;24(12):651-663. doi: 10.2217/pgs-2023-0109. Epub 2023 Aug 23.

Abstract

Metformin, a hypoglycemic drug for Type 2 diabetes mellitus, shows variability in pharmacokinetics and response due to membrane transporters. This study followed 34 Type 2 diabetes mellitus patients on metformin treatment. Genetic variants in 11 metformin transport-related genes were analyzed, revealing associations. Specifically, SLC47A1 rs2289669 A/A and SLC22A4 rs1050152 T/T genotypes correlated with glycated hemoglobin values at 6 months. SLC47A1 rs2289669 G/A genotype influenced glucose levels at 6 months, while SLC29A4 rs3889348 A/A, SLC47A1 rs2289669 A/A, SLC22A4 rs1050152 C/T and SLC47A2 rs12943590 A/A genotypes were linked to glucose levels at 12 months. Additionally, ABCB1 rs2032582 C/A and ABCG2 rs2231137 C/T genotypes impacted cholesterol levels at 12 months. These findings shed light on metformin response determinants, offering insights for further research.

Keywords: Type 2 diabetes mellitus; metformin; pharmacogenetics; polymorphisms; transporters.

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / genetics
  • Glucose / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin* / pharmacokinetics
  • Metformin* / therapeutic use
  • Organic Cation Transport Proteins / genetics
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide / genetics

Substances

  • Metformin
  • Organic Cation Transport Proteins
  • Hypoglycemic Agents
  • Glucose