Glycaemic responses to metformin monotherapy by SNP clusters in patients with type 2 diabetes

This study retrospectively investigates the association between polygenic risk scores (PRS) derived from SNP clusters and glycaemic response to metformin in patients with newly diagnosed T2D.

Utilizing a dataset from the Taiwan Precision Medicine Initiative, we evaluated alterations in fasting glucose (FBG) and glycated haemoglobin (HbA1c) in individuals newly diagnosed with T2D who underwent metformin monotherapy for a duration of 6 months. Glycaemic responses between those in the bottom 20% of PRS (Q1) and the top 20% of PRS (Q5) for each of the SNP clusters and for the combination of two clusters were analysed.

In responses to metformin monotherapy, significant differences of FBG levels were detected in Q1 as compared to Q5 in individuals of PRS derived from the cluster of beta-cell dysfunction with a positive association with proinsulin (Beta cell +PI) (p = 0.005) and the cluster of beta-cell dysfunction with a negative association with proinsulin (Beta cell -PI) (p = 0.003). Moreover, lower FBG levels on treatment were observed in those with both Q1 than those with both Q5 in the PRS derived from the two clusters of beta cell dysfunction (p = 0.002). Significantly reduced HbA1c values were documented in the Q1 in comparison to the Q5 within the cluster of Beta cell -PI (p = 0.002).

These findings suggest that PRS derived from beta-cell dysfunction clusters may help predict glycaemic response to metformin and support the potential for genetically guided treatment in T2D.