Introduction and Objective: Glycemic responses to metformin based on 8 SNP clusters in diabetes individuals, published by Suzuki (Nature, 2024), are unknown. Employing dataset from part of Taiwan Precision Medicine Initiative (TPMI), we explored the glycemic responses to metformin by quintile SNP cluster scores.
Methods: Tracking EMR from a medical center in Taiwan, we analyzed changes of fasting glucose and HbA1c, based on SNP clusters, in newly diagnosed type 2 diabetes who received metformin monotherapy for 6 months. (Fig. 1). GEE was used to compare the glycemic responses in those with Q1 vs. Q5 in each or two SNP clusters.
Results: Significant reduction of fasting glucose (FG) (p=0.007) and HbA1c (p<0.001) in those carrying Q1 vs. Q5 in beta cell dysfunction with negative proinsulin (BDNP). Greater lowering of FG (p=0.008) and marginally lowering of HbA1c (p=0.079) in those carrying Q1 vs. Q5 in beta cell dysfunction with positive proinsulin (BDPP). When considering both clusters together, diabetes subjects having clusters of both BDNP and BDPP showed better FG reduction in Q1 as compared to Q5 (p=0.015). Diabetes subjects carrying clusters of both metabolic syndrome and BDNP had greater HbA1c reduction in Q1 compared to Q5 (p=0.013).
Conclusion: We identified that SNP clusters with BDNP and BDPP, and metabolic syndrome, contributed to glycemic responses to metformin monotherapy in patients with type 2 diabetes.
C. Liao: None. T. Hsiao: None. J.I. Rotter: None.
National Health Research Institutes, Taiwan (MG-112-PP-18, MG-113-PP-18)
