Association of the SLC47A1 Gene Variant With Responses to Metformin Monotherapy in Drug-naive Patients With Type 2 Diabetes

Context: Although metformin is the first-line treatment for type 2 diabetes, the blood sugar-lowering effect of metformin varies among populations. SLC47A1 plays an important role in metformin pharmacokinetics and pharmacodynamics. Objective: We performed a systematic review and meta-analysis to investigate the association between SLC47A1 rs2289669 (G>A) and the metformin response in drug-naive patients with type 2 diabetes. Methods: Studies published until January 27, 2022, were retrieved from Cochrane CENTRAL, Embase, PubMed, and Web of Science. Two reviewers independently screened titles, abstracts, and full-text articles. Studies conducted in newly diagnosed or drug-naive patients with type 2 diabetes who received metformin monotherapy were included. A total of 6 studies involving 953 patients were included in this meta-analysis. We extracted the study characteristics and changes in glycated hemoglobin (HbA1c) levels before and after treatment according to the SLC47A1 rs2289669 genotype. Changes in HbA1c levels were analyzed using mean differences (MDs) and 95% CIs. SLC47A1 rs2289669 was associated with changes in HbA1c levels (A carrier vs GG; MD=-0.55; 95% CI,-0.91 to-0.20; I²=63%). The sensitivity analysis yielded similar results to the main analysis (MD range,-0.64 to-0.37). When comparing all 3 genotypes, there were significant differences in HbA1c level changes between AA vs GG and GA vs GG, but not in GA vs AA. Conclusion: This meta-analysis showed that SLC47A1 rs2289669 is associated with the glycemic response to metformin in drug-naive patients with type 2 diabetes.