The EXSCEL trial investigated the cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes.1
14,752 patients with type 2 diabetes, with or without previous cardiovascular disease, were randomized to receive extended-release exenatide at a dose of 2 mg or matching placebo once weekly.1
The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and occurred in 11.4% of patients in the exenatide group and 12.2% of those given placebo (HR, 0.91; 95% CI 0.83-1.00).1
Thus, major adverse cardiovascular events did not differ significantly between patients who received exenatide or placebo.1
However, GLP-1 receptor agonists may provide renal benefit in those at high risk of worsening kidney disease.2
How was this study conducted?
This was a post-hoc analysis of data from the EXSCEL trial.
The primary outcomes were annual rate of eGFR decline (eGFR slope) and percent change in urine albumin to creatinine ratio (UACR).
The effects of exenatide once weekly (EQW) on eGFR slope and UACR as a function of baseline UACR were studied in 3503 EXSCEL participants (23.7%) with eGFR data available and 2828 participants (19.2%) with UACR change data available.
Exenatide 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% 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.
Exenatide 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) (Fig. 1).
The effect of exenatide on UACR was also consistent across subgroups defined by baseline eGFR, history of cardiovascular disease, use of renin-angiotensin-aldosterone system inhibitors, systolic blood pressure and body mass index.
How does this study impact clinical practice?
Exenatide treatment slowed the progression of eGFR decline in participants with elevated baseline UACR (>100 mg/g) but not among those with lesser degrees of UACR.
The effect of EQW on eGFR slope was consistent regardless of the presence or absence of other risk markers of chronic kidney disease progression.
van der Aart-van der Beek AB, Clegg LE, et al. Effect of once-weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: a post hoc analysis of the EXSCEL trial. Diabetes Obes Metab. 2020 Aug 17. doi: 10.1111/dom.14175. Epub ahead of print. PMID: 32803900.
This is a highlights summary of an oral session given at the EASD 2020 Virtual Meeting and presented by:
Annemarie B. Van der Aart, PharmD
Clinical Pharmacology, University of Groningen, The Netherlands
The presenting authors of the original session had no part in the creation of this conference highlights summary.
The content is produced by Infomedica. The summary text was drafted by Patrick Moore, PhD, and reviewed by Marco Gallo, MD, an independent external expert, and approved by Florian Toti, MD, the scientific editor of the program.