Prediction and validation of exenatide risk marker effects on progression of renal disease: Insights from EXSCEL

AIM: To assess whether the previously developed multivariable risk prediction framework (PRE score) could predict the renal effects observed in the EXSCEL cardiovascular outcomes trial using short‐term changes in cardio‐renal risk markers. MATERIALS AND METHODS: Changes from baseline to 6 months in HbA1c, systolic blood pressure (SBP), body mass index (BMI), haemoglobin, total cholesterol, and new micro‐ or macroalbuminuria were evaluated. The renal outcomes were defined as a composite of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) or end‐stage renal disease (ESRD). Relationships between risk markers and long‐term renal outcomes were determined in patients with type 2 diabetes from the ALTITUDE study using multivariable Cox regression analysis, and then applied to short‐term changes in risk markers observed in EXSCEL to predict the exenatide‐induced impact on renal outcomes. RESULTS: Compared with placebo, mean HbA1c, BMI, SBP and total cholesterol were lower at 6 months with exenatide, as was the incidence of new microalbuminuria. The PRE score predicted a relative risk reduction for the 30% eGFR decline + ESRD endpoint of 11.3% (HR 0.89; 95% CI 0.83–0.94), compared with 12.7% (HR 0.87; 0.77–0.99) observed risk reduction. For the 40% eGFR decline + ESRD endpoint, the predicted and observed risk reductions were 11.0% (HR 0.89; 0.82–0.97) and 13.7% (HR 0.86, 0.72–1.04), respectively. CONCLUSIONS: Integrating short‐term risk marker changes into a multivariable risk score predicted the magnitude of renal risk reduction observed in EXSCEL.