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Canagliflozin’s Efficacy and Safety For Delaying and Possibly Preventing ESKD

Nov 23, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Andrew Daoud, PharmD Candidate, Florida A&M University

Preventing ESKD (end stage kidney failure): Kidney failure is an enormous concern for people with T2D and DKD. This analysis confirms canagliflozin can slow its progression and have an impact on patients regardless of their level of kidney function.

Innovative kidney disease medications are providing a lifeline for patients with different kidney diseases. Loss of kidney functioning due to diseases such as diabetic nephropathy and type 2 diabetes is common. 


In  September 2019, canagliflozin was approved by the U.S. Food & Drug Administration (FDA) to reduce the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for heart failure (HHF) in adults with T2D and DKD with a certain amount of protein in the urine. The approval was based on the Phase 3 CREDENCE study, which was stopped prematurely because it met the prespecified criteria for efficacy. In CREDENCE, canagliflozin 100 mg demonstrated a 30 percent reduction in the relative risk of the primary composite endpoint (ESKD, doubling of serum creatinine, and renal or CV death). Results also showed canagliflozin reduced the risk of secondary CV endpoints, including a 39 percent reduction in the relative risk of HHF. Overall, the incidence rates of adverse events and serious adverse events were lower for canagliflozin compared to placebo.

In a landmark announcement, canagliflozin was found to consistently reduce the risk of renal and cardiovascular events in patients with different levels of kidney functioning, as announced by Janssen Pharmaceutical Company. The efficacy and safety levels of canagliflozin from the findings provide physicians with the much-needed confidence to prescribing canagliflozin in the broadest range of kidney functioning otherwise referred to as estimated glomerular filtration rates (eGFR). In patients with eGFR 30 to <45 mL/min/1.73 m2, treatment with canagliflozin compared to placebo reduced the primary composite endpoint by 25 percent (events occurred in 72.2 vs 95.4 participants, respectively, per 1000 patient-years; hazard ratio [HR]: 0.75; 95 percent confidence interval [CI]: 0.59-0.95) and the renal-specific composite endpoint by 29 percent (events occurred in 51.6 vs 71.7 participants, respectively, per 1000 patient-years; HR: 0.71; 95 percent CI: 0.53-0.94).

The new-found confidence in prescribing canagliflozin, according to the article, is based on the existing prevalence of kidney function or eGFR. Estimates indicate that around 200 million individuals are affected by diabetic nephropathy, which is also the fifth leading and increasing cause of death in the world.  The findings provide renewed hope given the deadly effects of loss of kidney functioning. Without urgent intervention, the morbidity and mortality rate increases and would have extreme consequences for individuals with eGFR <60 mL/min/1.73 m2.

The FDA approved canagliflozin in September 2019 as a means to mitigate the risks of end-stage kidney disease, coronary artery disease, doubling the serum creatinine, and reducing the risk of hospitalization due to heart failure among others. Getting the approval of the FDA means the drug has been tested to determine the benefits and the risks. As a result, getting the nod of the FDA indicates that the benefits outweigh the risks, thereby meaning that canagliflozin is safe to use.

Canagliflozin can be used to lower blood sugar levels when complemented with diet and exercise in adults with type 2 diabetes. Secondly, it assists in mitigating cardiovascular events such as heart attacks or stroke or even death. Thirdly, it can be used for various kidney needs such as reducing the risk of worsening of the kidney function, reducing the effects of diabetic kidney disease and also cutting back on the need for hospitalization for heart failure, particularly in adults. 

However, like all prescription medications, it is important to be wary of potential side effects of canagliflozin, which can include dehydration, vaginal yeast infections, ketoacidosis, urinary infections, and a low risk for amputations.

Practice Pearls

  • Canagliflozin is the only diabetes medicine indicated to slow the progression of diabetic nephropathy (also known as DKD) and reduce the risk of hospitalization for heart failure in patients with type 2 diabetes (T2D) and DKD.
  • Canagliflozin benefits were seen in those with the most advanced renal insufficiency (eGFR <60 mL/min/1.73 m2).
  • By preventing ESRD and dialysis, it can save well over 50,000 dollars a year per patient.


Reference for “Canagliflozin’s Efficacy and Safety For Delaying and Possibly Preventing ESKD”:
NEJM Sept 2019

 Andrew Daoud, PharmD Candidate, Florida A&M University


See more about end stage kidney failure and preventing ESKD.