No significant effect of type 2 diabetes-related genetic risk scores on HbA1c levels after initiating metformin or sulfonylurea derivatives.

AIMS: To explore the added value of diabetes-related genetic risk scores to readily available clinical parameters in the prediction of HbA1c levels after initiation of glucose-regulating drugs.

MATERIALS AND METHODS: Cohort study including people with type 2 diabetes (T2DM) from the GIANTT database initiating metformin or sulfonylurea derivatives, and for whom blood samples were genotyped. The primary outcome was HbA1c level at 6-months adjusted for baseline HbA1c. Genetic risk scores (GRS) were based on SNPs linked to insulin sensitivity, beta-cell activity, and T2DM risk in general. Associations were analyzed by multiple linear regression to assess whether adding the risk scores increased the explained variance of a prediction model that included age, gender, diabetes duration, and cardio-metabolic biomarkers.

RESULTS: We included 282 patients initiating metformin and 89 patients initiating sulfonylurea derivatives. In the metformin prediction model, only diabetes duration of more than 3 months when starting metformin was associated with 2.7 mmol/mol higher HbA1c. For sulfonylurea derivatives, no significant clinical predictors were identified. Addition of the GRS linked to insulin sensitivity (for metformin), beta-cell activity (for sulfonylurea derivatives), and T2DM risk (for both) to the models did not improve the explained variance significantly (22% without vs. 22% with GRS) for the metformin and (14% without vs. 14 with GRS) for the sulfonylurea derivatives model, respectively.

CONCLUSION: This study did not indicate a significant effect of genetic risk scores related to T2DM in general or to the drugs' mechanism of action for prediction of inter-individual HbA1c variability in the short-term after start of metformin or sulfonylurea derivatives. This article is protected by copyright. All rights reserved.