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.
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