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Renal Outcomes After Canagliflozin Use in Patients with Type 2 Diabetes

Jul 27, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Usif Darwish, PharmD Candidate, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences

With diabetes mellitus the leading cause of end-stage renal disease (ESRD) worldwide, what are the renal outcomes after canagliflozin use in type 2?

With the prevalence of type 2 Diabetes Mellitus (DM) reaching global proportions, patients are becoming increasingly burdened by the comorbidities that are directly caused by DM. Renal failure is one such comorbidity that is becoming increasingly problematic and burdensome to both healthcare institutions and the patients they are treating. According to the International Diabetes Federation, there has been a 3-fold increase in the number of people living with diabetes from the year 2000 to 2017. To quantify this upward trend, the global prevalence of DM in 2000 was 151 million people. In 2017, there was a total of 425 million people around the world living with diabetes, and researchers are predicting that the upward trend will continue unless people around the world change the habits that they have adopted. Diabetes mellitus is the leading cause of end-stage renal disease (ESRD), with an estimated 3 million diabetes patients affected worldwide. 


Due to the damage diabetes causes to the kidneys, it is important to initiate patients on a renal protective agent that can delay the damage. In the early 2000s, ACE’s were approved as a renal protective therapy for patients with diabetes mellitus. Researchers are seeking new agents that may yield better renal outcomes for this ever so vulnerable population. Through research done for cardiovascular efficacy and safety, it was found that Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors showed favorable cardiovascular safety, and patients who were placed on an SGLT2 Inhibitor were shown to experience fewer cardiovascular events. This study, however, could not yield reputable results due to the low sample size of the patients who had both CVD and ESRD. 

Through the use of a double-blind, multicentered, randomized control trial, the researchers split 4401 patients across 34 countries into two groups. The first group was the canagliflozin group, while the second was the placebo-controlled group. The mean GFR and A1C of the sample population were 56.2 mL/min and 8.6% respectively. The event rate of the primary outcome was found to be significantly lower in patients taking canagliflozin compared to that of the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The primary outcome criteria include ESRD, the doubling of the SCr level, or death in association with cardiovascular or renal complications (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01). The secondary outcomes of the canagliflozin group were significant in the reduction of the relative risk when compared to that of the placebo group (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001). The secondary outcome criteria include CV death or hospitalization due to heart failure, MI, or stroke. The relative risk of ESRD in the canagliflozin group was met with a marked reduction of 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002), without an increase to the adverse effect profile of the pharmacological group when compared to that of the placebo group.  

Although ACE’s were found to be renal protective in the early 2000s, it is becoming increasingly important for researchers and providers to continue the search for new agents that can help decrease the incidence of morbidity and mortality. The SGLT2 Inhibitor, canagliflozin, was found to be renal protective and reduced cardiovascular event risk in patients who were found to be predisposed. In the article, it is mentioned that there were similar trials that analyzed the effects of other SGLT2 Inhibitors such as dapagliflozin and empagliflozin. Dapagliflozin was found to be non-inferior to placebo, while empagliflozin was found to be the superior therapy, in comparison to the placebo-controlled group. 

Practice Pearls:

  • According to the National Kidney Foundations guidelines KDIGO: Kidney Disease Improving Global Outcomes, Kidney Failure can be defined as a GFR of less than 15 mL/min
  • There are two possible treatment paths to kidney failure, dialysis or a kidney transplant. 
  • This article highlights just a few complications that diabetes patients become predisposed to once their A1C reaches diagnosable levels and the most favorable treatments that should be considered. 


References: Renal Outcomes After Canagliflozin Use in Patients with Type 2 Diabetes

European Society of Cardiology. (2019, April). Global statistics on diabetes. Retrieved June 29, 2019, from https://www.escardio.org/Sub-specialty-communities/European-Association-of-Preventive-Cardiology-(EAPC)/News/global-statistics-on-diabetes

National Kidney Federation. (2013). CKD Evaluation and Management. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease,3(1). doi:10.1038/kisup.2012.73

Perkovic, V., Jardine, M., Neal, B., Bompoint, S., & Heerspink, H., … (June 13, 2019). Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy, 380(24). doi:10.1056/NEJMoa1811744


Usif Darwish, PharmD Candidate, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences