Genetic determinants of variable anti-diabetic therapy responses across diverse populations with type 2 diabetes mellitus: a systematic review and meta-analysis

Aim: This study explores the relationship between gene polymorphisms and glycemic responses across ethnic populations and identifies optimal therapy combinations for glycemic control. However, the definition of glycemic response varied across included studies (e.g., HbA1c <7 %, or >0.5 % reduction), which may affect the comparability and interpretation of pooled data. Methods: Pooled odds ratios (ORs) with 95 % CI were used for binary glycemic outcomes, while pooled standardized mean differences (SMDs) with 95 % CI were applied to continuous glycemic outcomes. Heterogeneity was assessed with I2 and Cochran Q tests. Results: Of 43 articles screened, 36 studies involving 10 genes and 34 SNPs were included. Significant associations were found between improved glycemic response and the following variants: SLC22A1 rs622342, SLC47A2 rs12943590, TCF7L2 rs7903146, SLC22A1 rs12208357, and ABCC8 rs757110 (p < 0.05). In treatment analysis, Arabian, Indian, Mestizo, and Persian populations showed significant HbA1c reductions with biguanide monotherapy (p < 0.05). Arabian populations also exhibited significant reductions with biguanide-sulfonylurea combination therapy. Conclusion: Glycemic responses to anti-diabetic drugs vary across ethnic groups and are influenced by genetic variants. These findings support the need for personalised, genotype-guided therapy to improve glycemic control. Further research is necessary to explore broader drug classes and demographic factors.

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