EASD 2020 Highlights

Conference summaries


T2D TREATMENT

Once-weekly exenatide effects on eGFR slope and UACR as a function of baseline UACR: an EXSCEL trial post-hoc analysis

Presented by:

Annemarie B. Van der Aart, PharmD


  • Exenatide treatment slows eGFR decline in patients with baseline UACR >100 mg/g.
  • The effects of exenatide on albuminuria were consistent across all subgroups, and was independent of baseline albuminuria or other markers of progression of CKD.

What do we already know about this topic?

  • 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.

What does this study add?

  • 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.

Perspectives

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.


References

References


  1. Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017 Sep 28;377(13):1228-39.
  2. Greco EV, Russo G, Giandalia A, et al. GLP-1 receptor agonists and kidney protection. Medicina (Kaunas). 2019 May 31;55(6):233.

 

Related content

  • Górriz JL, Soler MJ, Navarro-González JF, et al. GLP-1 receptor agonists and diabetic kidney disease:a call of attention to nephrologists. J Clin Med. 2020 Mar 30;9(4):947.
  • 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.


Acknowledgements

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.


DIABETES & PREGNANCY

20 years HAPO Study: What have we learned so far?

Presented by: Patrick M. Catalano, MD
Expert commentary by Elizabeth O. Buschur, MD

DIABETES & HF

Empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial

Presented by: Javed Butler, MD; Milton Packer, MD; Stefen D.Anker, MD; Gerasimos Filippatos, MD; Faiez Zannad, MD
Expert commentary by Prof. Francesco Giorgino

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