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CREDENCE Trial – Overlooked Benefits In Preventing CVD 

Mar 3, 2020
Editor: Steve Freed, R.PH., CDE

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

SGLT2 Inhibitors and their use for preventing cardiovascular diseases: new CREDENCE analysis. 

As more and more diabetes medications hit the market, it is essential to know what the potential benefits and adverse effects of the medicines are. Sodium-Glucose CoTransporter-2 (SGLT2) Inhibitors are a newer drug class that has  shown great promise to the diabetes community. SGLT2 Inhibitors are known to reduce the risk of renal failure and chronic kidney disease, which are two conditions that significantly affect diabetic patients. However, provider knowledge on the effects of SGLT2 inhibitors and primary prevention of cardiovascular disease outcomes is still very much in the dark. In the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial, or CREDENCE, SGLT Inhibitors proved beneficial in patients with an increased risk of renal and cardiovascular complications. The authors of the article, however, would like to analyze the relationship between SGLT Inhibitors and primary and secondary prevention risk of cardiovascular disease in patients with Chronic Kidney Disease (CKD) patients. Diabetic patients are prone to develop CKD in the later years of their lives due to the progressive degradation of the renal function. This, in turn, can increase the risk of cardiovascular diseases and, ultimately, death. The focus of the published article is to analyze the CREDENCE trial results further, detailing the outcomes in patients with known CVD and those without.  


The CREDENCE trial was a double-blinded, randomized control trial that took place in multiple centers across the world, the details of which have been published previously. The inclusion criteria of the study included those who were 30 years of age or higher, that were diagnosed with type 2 diabetes and had an A1C of 6.5% to 12.0%. Finally, to be eligible, the patients needed a diagnosis of established CKD and albuminuria. Participants were to be on maximum ACE therapy for at least four weeks before randomization. All other treatments were excluded. Participants of the CREDENCE Trial were followed through visits for 26 weeks and then alternated to phone calls every 13 weeks after that. The mean follow-up for the 4,401 total participants was 2.62 years, and the trial spanned 34 countries. 

The cardiovascular outcomes for the canagliflozin group proved to be beneficial in Primary and Secondary Prevention. As noted by the researchers, patients in the placebo group were at an increased risk of CV death or hospitalization for heart failure, when compared to those in the SGLT2 group (15.1% vs. 7.9%; HR, 1.95; 95% CI, 1.51–2.53). When the researchers analyzed incidence in Major Cardiovascular Events (MACE), it was found that canagliflozin showed a significant reduction in occurrence (16.1% vs. 8.3%; HR, 1.97; 95% CI, 1.53–2.54). Canagliflozin was found to reduce MACE in the primary prevention group (HR, 0.68; 95% CI, 0.49–0.94), but failed to do so in the secondary group, as the data was not significant.  

In the CREDENCE trial, canagliflozin was shown to have significant benefits in the primary prevention of cardiovascular events and MACE. Although previous studies suggest that SGLT2 inhibitors can only benefit those with established CVD, Kenneth Mahaffey, MD, and his colleagues at Stanford Center for Clinical Research have shed light on the added benefits that were overlooked in those studies. The data showed consistency in the prevention of primary and secondary MACE in patients with T2D and CKD. Mahaffey notes that this result of primary prevention in SGLT2 inhibitors is the first of its kind in an antihyperglycemic sense. Although secondary prevention data did not show significance, it is essential to note that the data was consistent and that future studies with larger participant populations must be conducted.  

Practice Pearls: 

  • Previous studies suggest that SGLT2 inhibitors can benefit those with established cardiovascular disease.  
  • Using the data set forth from the CREDENCE trial, the researchers observed a significant reduction in cardiovascular risk when a patient was placed on an SGLT2 inhibitor, and consistent reduction of risk in secondary prevention patients. 
  • This is significant and can broaden the scope of SGLT2 Inhibitor use. Patients with established CKD and CVD can benefit significantly from the initiation of an SGLT2 inhibitor.  


Mahaffey, Kenneth W., et al. “Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups: Results from the Randomized CREDENCE Trial.” Circulation, 2019, doi:10.1161/circulationaha.119.042007. 


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