Identification of Clinical and Pharmacogenetic Factors Influencing Metformin Response in Type 2 Diabetes Mellitus

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::

• metformin
• pharmacogenetics
• polymorphisms
• transporters
• Type 2 diabetes mellitus

Author contributions

Conceptualization: N Pérez-Gómez and M Saiz-Rodríguez; methodology: M Saiz-Rodríguez; data curation: MD Fernández-Ortega, M Elizari-Roncal, E Santos-Mazo, L Maza-Pereg, N Pérez-Gómez and M Saiz-Rodríguez; writing – original draft preparation: M Saiz-Rodríguez and N Pérez-Gómez; writing – review and editing: N Pérez-Gómez, MD Fernández-Ortega, M Elizari-Roncal, E Santos-Mazo, L Maza-Pereg, S Calvo, R Alcaraz, A Sanz-Solas, R Vinuesa and M Saiz-Rodríguez; supervision: M Saiz-Rodríguez. All authors have read and agreed to the published version of the manuscript.

Financial & competing interests disclosure

This project was financed by the Regional Health Management of Castilla y León (GRS 2432/A/21). M Saiz-Rodríguez research was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation through the Sara Borrell Program (CD21/00022). A Sanz-Solas’s contract was funded by Fundación hna 2nd edition of the Scientific Health Research Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Institutional review board

The study was conducted in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of Health Care Area of Burgos and Soria.

Informed consent

Informed consent was obtained from all subjects involved in the study.

Data availability

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to confidentiality.

Additional information

Funding

This project was financed by the Regional Health Management of Castilla y León (GRS 2432/A/21). M Saiz-Rodríguez research was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation through the Sara Borrell Program (CD21/00022). A Sanz-Solas’s contract was funded by Fundación hna 2nd edition of the Scientific Health Research Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.