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. 2023 Aug 23:16:2523-2535.
doi: 10.2147/DMSO.S426632. eCollection 2023.

Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes

Abraham Degaga  1   2 , Sisay Sirgu  3 , Hasniza Zaman Huri  2 , Maw Shin Sim  4 , Tedla Kebede  5 , Birhanemeskel Tegene  6 , Navin Kumar Loganadan  7 , Ephrem Engidawork  1 , Workineh Shibeshi  1
Affiliations

Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes

Abraham Degaga et al. Diabetes Metab Syndr Obes. .

Abstract

Objective: This study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM).

Patients and methods: A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05.

Results: The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level.

Conclusion: This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.

Keywords: Ethiopia; Met420del; SLC22A1 gene; T2DM; glycemic response; metformin.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Independent Samples Mann–Whitney U-test between genotypes of Met420del variant of SLC22A1gene (rs72552763) and absolute reductions in HbA1C (A) and in FBG (B) following three months of metformin treatment.
Figure 2
Figure 2
Independent Samples Mann–Whitney U-test between genotypes of Met420del variant of SLC22A1gene (rs72552763) and median HbA1c (A) and FBG (B) levels following three months of metformin treatment.
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