Even in well-controlled T2D, canagliflozin offers CV, renal benefit

  • Cannon CP & al.
  • Circulation
  • 11 Nov 2019

  • International Clinical Digest
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Takeaway

  • Treatment of patients with chronic kidney disease and/or atherosclerotic cardiovascular (CV) disease is warranted even in patients who have type 2 diabetes (T2D) that is “well-controlled” (HbA1c 6.5%-7.0%).

Why this matters

  • Initial clinical trials included mostly patients with baseline HbA1c >7%, so current guidelines have recommended sodium glucose co-transporter 2 inhibitors (SGLT2is) as add-on therapy for patients with HbA1c >7%.

Study design

  • Analysis of results from the double-blind, randomized Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial by baseline HbA1c: 650 with 
  • Overall, canagliflozin (Invokana) was tied to a significant reduction in the primary composite outcome (end-stage kidney disease, serum creatinine doubling, or renal or CV death) and other CV endpoints including hospitalization for heart failure (HHF).  
  • Funding: Janssen Research and Development, LLC.

Key results

  • No differences in primary outcome reduction across baseline HbA1c levels, with HRs 0.63, 0.84, and 0.63 for interaction=.277).
  • No differences by baseline HbA1c across composite or singular secondary outcomes, including HHF (0.41, 0.73, and 0.59, respectively, Pinteraction=.462).
  • No differences in serious adverse events by baseline HbA1c, including amputation, hypoglycemia, or acute kidney injury.  

Limitations

  • Early termination may have limited power for some secondary outcomes.