No significant association of type 2 diabetes‐related genetic risk scores with glycated haemoglobin levels after initiating metformin or sulphonylurea derivatives

AIM: To explore the added value of diabetes‐related genetic risk scores (GRSs) to readily available clinical variables in the prediction of glycated haemoglobin (HbA1c) levels after initiation of glucose‐regulating drugs. MATERIALS AND METHODS: We conducted a cohort study in people with type 2 diabetes (T2DM) from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database who initiated metformin (MET) or sulphonylurea derivatives (SUs) and for whom blood samples were genotyped. The primary outcome was HbA1c level at 6 months, adjusted for baseline HbA1c. GRSs were based on single nucleotide polymorphisms linked to insulin sensitivity, β‐cell activity, and T2DM risk in general. Associations were analysed using multiple linear regression to assess whether adding the GRSs increased the explained variance in a prediction model that included age, gender, diabetes duration and cardio‐metabolic biomarkers. RESULTS: We included 282 patients initiating MET and 89 patients initiating SUs. In the MET prediction model, diabetes duration of >3 months when starting MET was associated with 2.7‐mmol/mol higher HbA1c level. For SUs, no significant clinical predictors were identified. Addition of the GRS linked to insulin sensitivity (for MET), β‐cell activity (for SUs) and T2DM risk (for both) to the models did not improve the explained variance significantly (22% without vs. 22% with GRS) for the MET and (14% without vs. 14% with GRS) for the SUs model, respectively. CONCLUSION: This study did not indicate a significant effect of GRS related to T2DM in general or to the drugs' mechanism of action for prediction of inter‐individual HbA1c variability in the short term after initiation of MET or SU therapy.