# 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

## TL;DR

This study compares long-term diabetes complications when using different second-line treatments, finding that SGLT2i drugs reduce risks more than other options.

## Contribution

The study introduces a real-world microsimulation model to compare long-term outcomes of second-line diabetes treatments in routine clinical practice.

## Key findings

- SGLT2i treatment reduces the predicted probability of end-stage kidney disease more than sulphonylureas and DPP4i.
- SGLT2i also lowers the risk of heart failure hospitalization and diabetic eye disease compared to other treatments.
- Lower-extremity amputation risks remain similar across all treatment types.

## Abstract

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.

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).

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.

For a general T2DM population, second‐line treatment with SGLT2i rather than SU or DPP4i can reduce the probability of complications within 5 years.