Does CVD protection from SGLT-2Is and GLP-1RAs vary by sex?

  • Singh AK & al.
  • Diabetes Metab Syndr
  • 26 Feb 2020

  • curated by Miriam Tucker
  • Clinical Essentials
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Takeaway

  • A meta-analysis has shown a significant reduction in major adverse cardiac events (MACEs) with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in both sexes, but MACE differences with sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) were significant only in men.

Why this matters

  • Recent European/American consensus guidelines recommend SGLT-2Is or GLP-1RAs as second-line drugs after metformin or as first-line drugs in patients with type 2 diabetes (T2D) with established cardiovascular disease (CVD), based on aggregate data from randomized, controlled, cardiovascular outcome trials (CVOTs).
  • Sex differences not previously assessed. 

Study design

  • Meta-analysis of 3 CVOTs of SGLT-2Is (n=34,322) and 7 of GLP-1RAs (n=56,004) vs placebo.
  • Funding: None.

Key results

  • With SGLT-2Is, significant reduction seen in MACEs in men (HR, 0.90; P=.006) but not women (HR, 0.88; P=.06).
  • With GLP-1RAs, significant and similar reductions seen in men (HR, 0.88; P<.0001 and women>

Limitations

  • No individual patient data.
  • Moderate heterogeneity in GLP-1RA studies in women.
  • Unclear whether differential results relate to inadequate statistical power because of underrepresentation of women vs true sex difference.