Genetic and Clinical Determinants of Variation in Drug Response in Type 2 Diabetes: Insights From the Scottish and UK Biobank Cohorts
Authors' conclusion
Both clinical and genetic factors significantly contribute to inter-individual variability in T2D drug response.
Study context
- Population
- Patients with T2D initiating metformin, sulfonylureas, TZDs, DPP4i, SGLT2i or GLP-1RA11,615 and 8293 genotyped
- Participants
- 41,802 vs 9,371
- Comparison
- Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) vs UKBB
- GoDARTSn = 41,802
- UKBBn = 9,371
- Outcome
- Glycaemic response: change in HbA1c after treatment initiation
- Follow-up
- 12 months
Methodological detailstwo population-based cohorts, partitioned polygenic risk scores, linear regression within cohort and drug class
- Two population-based cohorts
- Partitioned polygenic risk scores
- Linear regression within cohort and drug class
Pooled result
As reported in the abstract
Determinants of HbA1c change
- Baseline HbA1c most strongly associated with glycemic response
- p < 0.001
- Higher overall T2D genetic risk: greater HbA1c reduction with sulfonylureas (β, meta-analysis)
- β = −0.46 mmol/mol, p = 0.013
- β-cell function clusters with sulfonylureas
- β = −0.57, p = 0.002
- Obesity-related variants with GLP-1RA
- β = −1.49, p = 0.04
- Liver-lipid variants with SGLT2 inhibitors
- β = −0.84, p = 0.05
- Bilirubin partitioned polygenic risk scores (pPRS) with DPP-4 inhibitors
- β = −0.69, p = 0.006
Original publication
Genetic and Clinical Determinants of Variation in Drug Response in Type 2 Diabetes: Insights From the Scottish and UK Biobank Cohorts. Diabetes Obes Metab. Published 1 September 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →