Validation of an algorithm for selection of SGLT2 and DPP4 inhibitor therapies in people with type 2 diabetes across major UK ethnicity groups: a retrospective cohort study.

Background: Routine clinical features of individual patients can potentially be used to guide selection of type 2 diabetes treatments. We aimed to evaluate a recently proposed treatment selection model predicting differences in glycaemic responses to SGLT2-inhibitors and DPP4-inhibitors across major UK ethnicity groups. Methods: We externally validated the SGLT2i-DPP4i model in UK primary care cohort (CPRD Aurum, 2013-2020) independent of the original model development cohort. Non-insulin treated individuals with type 2 diabetes were identified and categorised by major UK self-reported ethnicity groups: White, Black, South Asian and Mixed/Other. For each ethnicity group, we applied a closed testing procedure to assess whether model recalibration was required. After model updates, we assessed the calibration accuracy of predicted differences in glycaemic response (6-month change in HbA1c) between SGLT2i and DPP4i for each ethnicity group. Findings: SGLT2i (n = 57,749) and DPP4i (n = 87,807) initiations were identified amongst people of White (n = 114,287; 78.5%), Black (n = 6663; 4.6%), South Asian (n = 20,969; 14.4%) and Mixed/Other (n = 3637; 2.5%) ethnicities. Minor model adjustment was required to adjust for greater observed than predicted glycaemic responses to DPP4i (White-1.6 mmol/mol; Black-3.0 mmol/mol; South Asian-2.6 mmol/mol; Mixed/Other-2.6 mmol/mol). SGLT2i predictions did not require adjustment for non-White ethnicity groups. After model updates, average predicted HbA1c reduction was 3.7 mmol/mol (95% CI 3.5-3.9) greater with SGLT2i than DPP4i for those of White ethnicity; this was greater than for those of South Asian (2.1 mmol/mol (95% CI 1.6-2.6)), Black (0.6 mmol/mol (95% CI 0.5-1.7)) and Mixed/Other (2.6 mmol/mol (95% CI 1.4-3.8)) ethnicity groups. For all ethnicity groups, predicted differential glycaemic treatment effects were well calibrated. Interpretation: Our model for selection of SGLT2-inhibitor and DPP4-inhibitor therapies was accurate for all major self-reported ethnicity groups in a UK primary care cohort. Simple recalibration is beneficial to optimise performance and this is recommended prior to deployment of the model in new populations and settings. Funding: UK Medical Research Council, National Institute for Health and Care Research Exeter Biomedical Research Centre, and EFSD/Novo Nordisk.