Pharmacogenomic insights into OCT1, OCT3 Variants Affecting Metformin Efficacy in Type 2 Diabetes: A Systematic Review and Meta-Analysis

Type 2 diabetes mellitus (T2DM) poses a significant global health burden, particularly in India. Metformin is the first-line therapy for T2DM; however, substantial interindividual variability in glycemic response remains a clinical challenge. Genetic polymorphisms in organic cation transporter genes—OCT (Organic Cation Transporter)1 (SLC22A1), OCT2 (SLC22A2), and OCT3 (SLC22A3)—may influence metformin transport and therapeutic efficacy. This study aimed to evaluate the association between OCT1–OCT3 gene variants and glycemic response or pharmacokinetics of metformin in patients with T2DM. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted from 2022 to May 2025. Seven eligible studies investigating the relationship between OCT1–OCT3 polymorphisms and metformin response were included. Meta-analyses were performed using RevMan 5.4 and STATA, applying fixed- or random-effects models based on heterogeneity (I2). Effect sizes were reported as odds ratios (ORs) or mean differences (MDs, expressed as percentage change in HbA1c) with 95% confidence intervals. Study quality was assessed using the Newcastle– Ottawa Scale. Seven studies involving 1307 patients were included. OCT1 rs622342 (AA genotype) and rs628031 (G allele) variants were significantly associated with reduced glycemic response to metformin (MD = −0.58%; OR = 1.65). The OCT3 rs2292334 variant was also associated with poorer HbA1c reduction, while no significant association was observed for OCT2 rs316019. Subgroup analyses indicated stronger associations among Indian and South Asian populations. Egger’s test did not indicate significant publication bias. This meta-analysis suggests that selected OCT1 and OCT3 variants may influence metformin response in T2DM; however, findings should be interpreted cautiously because of limited and heterogeneous evidence.

Registration: Registration has been completed in PROSPERO (ID.NO. 1079016).

Cite this article as: Dalal VI. Pharmacogenomic insights into OCT1, OCT2, and OCT3 variants affecting metformin efficacy in type 2 diabetes: A systematic review and meta-analysis. Endocrinol Res Pract. Published online June 1, 2026. doi: 10.5152/erp.2026.25806.