Once-weekly exenatide in patients with type 2 diabetes and heart failure

  • Fudim M & al.
  • Circulation
  • 23 Sep 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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Takeaway

  • In patients with type 2 diabetes and with or without heart failure (HF), once-weekly exenatide (EQW) was well tolerated, but its benefits on reduction in all-cause death and first hospitalisation for HF (hHF) were attenuated in patients with baseline HF.
  • EQW use was associated with a lower risk for recurrent hHF.

Why this matters

  • In the recent Exenatide Study of Cardiovascular Event Lowering (EXSCEL), EQW showed a neutral effect on time to first hHF with no differential treatment effect on the primary endpoint of major adverse cardiovascular events by baseline HF status.
  • However, its effects on secondary endpoints of all-cause death and hHF have not been reported.

Study design

  • Pre-specified analysis of EXSCEL (n=14752) explored the effects of EQW on all-cause death, first hHF and repeat hHF in patients with (n=2389) and without baseline HF (n=12362).
  • In EXSCEL, 2389 patients with HF were randomly assigned to receive exenatide (n=1161) and placebo (n=1228).
  • Funding: Amylin Pharmaceuticals Inc.

Key results

  • EQW vs placebo group had a lower incidence of all-cause death (HR, 0.86; 95% CI, 0.77-0.97) and the composite of all-cause death or hHF (HR, 0.89; 95% CI, 0.80-0.99).
  • Based on stratification by presence or absence of baseline HF:
    • EQW vs placebo did not show reduction in all-cause death in patients with HF (HR, 1.05; 95% CI, 0.85-1.29).
    • In patients without HF, the risk for mortality was significantly reduced with EQW vs placebo (HR, 0.79; 95% CI, 0.68-0.92; Pinteraction=.031).
  • EQW use was associated with reduction in the composite of all-cause death or hHF in patients without HF (HR, 0.81; 95% CI, 0.71-0.93) but not in those with HF (HR, 1.07; 95% CI, 0.89-1.29; Pinteraction=.015).
  • Exenatide vs placebo group had a reduction in the risk for first plus recurrent hHF (HR, 0.82; 95% CI, 0.68-0.99; P=.038).

Limitations

  • Possible risk of bias.
  • Baseline HF status was clinically defined by the treatment team and was not formally adjudicated.