Effect of once‐weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: A post hoc analysis of the EXSCEL trial

The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on renal outcomes in patients with type 2 diabetes at high cardiovascular risk are modest or neutral. However, GLP-1RAs may confer clinical benefits in those at high risk of progressive renal function loss. We examined the effects of once-weekly exenatide (EQW) on estimated glomerular filtration rate (eGFR) slope and urinary albumin: creatinine ratio (UACR) as a function of baseline UACR in 3503 EXSCEL participants (23. 7%) with eGFR data available and 2828 participants (19. 2%) with UACR change data available. EQW improved eGFR slope assessed via mixed model repeated measures, compared with placebo, in participants with baseline UACR >100 mg/g (0. 79 mL/min/1. 73 m2 /year 95% confidence interval CI 0. 24-1. 34) and UACR >200 mg/g (1. 32 mL/min/1. 73 m2 /year 95% CI 0. 57-2. 06), but not at lower UACR thresholds. EQW reduced UACR, compared with placebo, assessed via analysis of covariance, consistently across subgroups with baseline UACR >30 mg/g (28. 2% reduction), baseline UACR >100 mg (22. 5% reduction) and baseline UACR >200 mg (34. 5% reduction). This post hoc EXSCEL analysis suggests that EQW reduces UACR, with improvement in eGFR slope specifically in participants with elevated baseline UACR.