Do SGLT2 inhibitors reduce atherosclerotic endpoints?

  • Sinha B & al.
  • Diabetes Ther
  • 14 Mar 2019

  • International Clinical Digest
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Takeaway

  • Primary benefit of sodium-glucose cotransporter-2 inhibitor (SGLT2is) appears to be reduction in hospitalization for heart failure (h[HF]) and possibly cardiovascular (CV) mortality, but not atherosclerotic CV disease.

Why this matters

  • A previous meta-analysis suggested that SGLT2is reduce atherosclerotic events in addition to other CV endpoints. 
  • Editorial called for SGLT2i use as first-line therapy after metformin in type 2 diabetes (T2D), even among patients at lower CV risk.

Study design

  • Meta-analyses of 3 CV outcome trials (n=34,322) and pooled phase 3 data for all available gliflozins (n=23,334), plus examination of supplementary materials, regulatory analysis, and mechanistic data.  
  • Funding: None.

Key results

  • HR for major adverse cardiac events (MACE) was statistically significant (0.89; P=.002).
  • Significant reduction in nonfatal myocardial infarction (MI) (0.87; P=.01) but no improvement for nonfatal stroke (1.01; P=.83).
  • In one trial, significant reduction in “CV death or hHF” composite endpoint (0.76; P<.001 but driven primarily by hhf vs cv death>
  • In phase 3 pooled analysis, significant results for MI (0.664; P=.014), CV death (0.637; P=.038), and hHF (0.360; P=.002).
  • Insignificant effects for MACE (0.832; P=.103) and stroke (1.172; P=.403).   

Limitations

  • Inclusion of short-duration studies.
  • Analysis of aggregate rather than individual patient data.