Oral semaglutide and cardiovascular risk profile in type 2 diabetes

  • Husain M & al.
  • N Engl J Med
  • 29 Aug 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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Takeaway

  • PIONEER 6 trial demonstrated that the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo in patients with type 2 diabetes (T2D).

Why this matters

  • Findings are consistent with cardiovascular outcomes trials of glucagon-like peptide-1 (GLP-1) receptor agonists, all of which confirmed the absence of excess cardiovascular risk.

Study design

  • PIONEER 6 trial randomly assigned 3183 patients (mean age, ≥66 years) with cardiovascular or chronic kidney disease to receive either oral semaglutide (n=1591) or placebo (n=1592).
  • Primary outcome: occurrence of major adverse cardiovascular events (MACEs: death from cardiovascular causes, non-fatal myocardial infarction or non-fatal stroke).
  • Funding: Novo Nordisk.

Key results

  • Patients in the oral semaglutide vs placebo group had lower:
    • MACEs (3.8% vs 4.8%; HR, 0.79; 95% CI, 0.57-1.11; P<.001 for non-inferiority>
    • death from cardiovascular causes (0.9% vs 1.9%; HR, 0.49; 95% CI, 0.27-0.92),
    • death from any cause (1.4% vs 2.8%; HR, 0.51; 95% CI, 0.31-0.84) and
    • non-fatal stroke (0.8% vs 1.0%; HR, 0.74; 95% CI, 0.35-1.57).
  • Oral semaglutide vs placebo group demonstrated higher:
    • non-fatal myocardial infarction (2.3% vs 1.9%; HR, 1.18; 95% CI, 0.73-1.90) and
    • gastrointestinal adverse events (6.8% vs 1.6%).