Background: Approximately 40% of patients do not achieve optimal therapeutic effects during the initial use of metformin as monotherapy for type 2 diabetes mellitus (T2DM). This suboptimal response may be influenced by genetic variation in the SLC22A1 gene, particularly the rs628031 polymorphism affecting the OCT1 transporter.

Objective: To investigate the effect of the SLC22A1 rs628031 Met408Val genetic variation on blood glucose profiles in patients, including HbA1c levels, fasting blood glucose (FBG), and 2-hour postprandial blood glucose (2h-PBG).

Methods: This observational study employed a prospective cohort design involving 123 T2DM patients receiving metformin monotherapy. The SLC22A1 rs628031 Met408Val polymorphism was analyzed using the PCR-RFLP method. The influence of this genetic variation on changes in HbA1c, FBG, and 2h-PBG levels was assessed by comparing baseline values to those at week 12.

Results: Genotyping of the SLC22A1 rs628031 Met408Val polymorphism revealed that 14% of participants had the AA allele, while 86% carried the AG or GG alleles. The AG-GG group exhibited significantly  reductions in HbA1c, FBG, and 2h-PBG levels compared to the AA group (p < 0.05).

Conclusion: The SLC22A1 rs628031 Met408Val polymorphism is associated with a reduced therapeutic response to metformin, as indicated by less favorable changes in HbA1c, FBG, and 2h-PBG.