How do the SGLT2is compare in reducing CV outcomes in T2D?

  • Täger T & al.
  • Heart Fail Rev
  • 20 Apr 2020

  • curated by Miriam Tucker
  • Clinical Essentials
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Takeaway

  • In patients with type 2 diabetes (T2D), empagliflozin is associated with a greater reduction in cardiovascular (CV) and all-cause mortality (ACM).
  • Empagliflozin, canagliflozin, and dapagliflozin all elicited similar reductions in heart failure (HF) worsening.

Why this matters

  • CV risk reduction with sodium-glucose cotransporter-2 inhibitors (SGLT2is) differs among trials.
  • Uncertainty remains about comparative efficacy of individual SGLT2is vs class effect.

Study design

  • Systematic review, meta-analysis of 64 trials with outcome data from 71,719 patients with T2D.
  • Funding: Projekt DEAL (open-access funding).

Key results

  • Significant reductions in CV mortality vs placebo (all relative risks; 95% CIs) with:
    • Canagliflozin: 0.85 (0.73-0.99). 
    • Empagliflozin: 0.61 (0.49-0.77).
  • In head-to-head comparisons for CV mortality, empagliflozin was superior to canagliflozin (0.72; 0.55-0.95) and dapagliflozin (0.63; 0.48-0.85).
  • Significant ACM reductions vs placebo with:
    • Canagliflozin: 0.85 (0.75-0.97). 
    • Empagliflozin: 0.67 (0.55-0.80).
  • Head-to-head, ACM reduction was steeper with empagliflozin vs canagliflozin (0.78; 0.62-0.98) or dapagliflozin (0.72; 0.58-0.90).
  • For worsening HF, vs placebo:
    • Canagliflozin: 0.62 (0.52-0.75).
    • Dapagliflozin: 0.75 (0.62-0.88). 
    • Empagliflozin: 0.66 (0.50-0.86). 
      • No differences among individual SGLT2is.

Limitations

  • 4 trials contributed the most patients.
  • Short follow-up (mean 40 weeks).
  • Most studies not designed as CV outcome trials.
  • Baseline CV risk varied across trials.
  • Meta-analysis differences may not be clinically meaningful.