Long-term outcomes following alternative second-line oral glucose-lowering treatments: Results from the real-world progression in type 2 diabetes mellitus United Kingdom (RAPIDS-UK) model

Abstract

Aims: To compare long-term complications for people with type 2 diabetes mellitus (T2DM) following second-line treatment in routine practice with sulphonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose co-transporter-2 inhibitors (SGLT2i) added to metformin. Materials and Methods: We used the RAPIDS microsimulation model to predict diabetes complications over 5 years after second-line treatment initiation. We combined information on ‘real-world’ treatment duration in England from the Clinical Practice Research Datalink with evidence on treatment effectiveness from Randomised Controlled Trials (RCTs). We estimated between-treatment differences in the probabilities of end-stage kidney disease (ESKD), heart failure hospitalisation (HF), diabetic eye disease, myocardial infarction (MI), and lower-extremity amputation (LEA). Results: The predicted probabilities of complications within 5 years were lower following second-line treatment with SGLT2i compared to SU and DPP4i. The mean (95% CI) difference (reduction) in the predicted probability of ESKD following SGLT2i versus SU was −0.81% (−0.89, −0.73), and for SGLT2i versus DPP4i the corresponding difference was −0.87% (−0.95, −0.79). The reduction in the probability of HF following SGLT2i versus SU was −0.90% (−1.01, −0.80), and for SGLT2i versus DPP4i it was −0.95% (−1.06, −0.84). The corresponding differences in the probabilities of diabetic eye disease following SGLT2i versus SU were −1.41% (−1.57, −1.26), and for SGLT2i versus DPP4i was −0.44% (−0.59, −0.29). The predicted probabilities of LEA were similar across treatments. Pre-existing CVD did not modify the predicted probabilities of complications. Conclusions: For a general T2DM population, second-line treatment with SGLT2i rather than SU or DPP4i can reduce the probability of complications within 5 years.