Cardiovascular safety of canagliflozin

Comparing risks with those of placebo


Adding canagliflozin to an existing therapy in patients with type 2 diabetes and high cardiovascular risk is just as safe as adding a placebo, but may possibly offer only marginally greater cardiovascular protection than placebo.
• Saving one patient from dying of a cardiovascular disorder, from a non-fatal cardiac infarction or from a non-fatal stroke requires that over 200 patients with diabetes and a high cardiovascular risk are treated with canagliflozin.
• The study discussed here found that diabetes patients treated with canagliflozin were at increased risk of leg, metatarsal or toe amputation, as well as of fractures and urogenital infections, compared to placebo.
• In view of its high cost, its limited clinically relevant cardiovascular benefit and its potential side effects, canagliflozin is currently not a therapeutic option that can be recommended for patients with type 2 diabetes.


  1. FDA Guidance for Industry - Diabetes Mellitus — EvaluatingCardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes. December 2008. Via: https://www.fda.gov/downloads/Drugs/Guidances/ucm071627.pdf.
  2. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377: 644-657. Commentaar in: N Engl J Med 2017; 377: 2098.
  3. Informatorium medicamentorum 2018. KNMP Den Haag. Via: kennisbank.knmp.nl.
  4. Productinformatie canagliflozine (Invokana®). Via: www.ema.europa.eu.
  5. Neal B, Perkovic V, Matthews DR, et al. Rationale, design and baseline characteristics of the CANagliflozin cardiovascular Assessment Study-Renal (CANVAS-R): a randomized, placebocontrolled trial. Diabetes Obes Metab 2017; 19: 387-93.
  6. EMA PRAC. SGLT2 inhibitors and lower limb amputation (canagliflozin, dapagliflozin,empagliflozin-containing medicines) EMA/PRAC/637349/2016. Via: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/002672/WC500230719.pdf.
  7. Fernández-Balsells MM, Sojo-Vega L, Ricart-Engel W. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377: 2098.
  8. Baglioni P. Canagliflozin and Cardiovascular and Renal Events in Type 2. Diabetes. N Engl J Med 2017; 377: 2097-8.
  9. Neal B, Perkovic V, Mahaffey KW, Fulcher G, Erondu N, Desai M, et al. Optimizing the analysis strategy for the CANVAS Program: A prespecified plan for the integrated analyses of the CANVAS and CANVAS-R trials. Diabetes Obes Metab 2017; 19: 926-935.
  10. Barents ESE, Bilo HJG, Bouma M, Van den Brink-Muinen A, Dankers M, Van den Donk M, et al. NHG-Standaard Diabetes mellitus type 2 (Vierde (partiële) herziening). Juni 2018. Via: www.nhg.org/standaarden.

The literature refers to the Dutch text

Authors

  • mw drs M.A.E. Nieuwhof, dr H.J.E.M. Janssens