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Treating Kidney Disease With Dapagliflozin

Apr 24, 2021
 
Editor: Steve Freed, R.PH., CDE

Author: A'Kira Shavers,  PharmD Candidate, South College School of Pharmacy

DAPA-CKD trial demonstrated that dapagliflozin helped patients with and without diabetes in improving kidney disease.

Many patients with chronic kidney disease are at a higher risk of adverse kidney and cardiovascular outcomes. The DAPA-CKD trial was designed to see the impact of Dapagliflozin Propanediol in patients with and without type 2 diabetes who had chronic kidney disease.  Dapagliflozin Propanediol, Farxiga, is a sodium-glucose co-transporter 2 inhibitor and an antidiabetic. Part of its specific action mechanism is to reduce the reabsorption of filtered glucose, lower the renal threshold for glucose, and increase urinary glucose excretion.  The actual effect of Dapagliflozin Propanediol in patients with chronic kidney disease is unknown. A renal function check is essential at the start and periodically throughout the duration to ensure the patient is not experiencing renal impairment, an estimated glomerular filtration rate  less than 60.  The FDA approves Farxiga for the use in patients with heart failure (class II through IV) with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure as well as in patients with type 2 diabetes with cardiovascular disease or multiple cardiovascular risk factors, to reduce the risk of hospitalization for heart failure.   

 

The trial had 4,304 participants who were randomly assigned to different groups.  The two groups consisted of one group receiving Dapagliflozin Propanediol 10mg daily, and the other group receiving a placebo. To be a part of the study, patients had to have a glomerular filtration rate of 25 to 75 mL per minute per 1.73 meters squared of body surface area and urinary albumin to creatine ratio of 200 to 5000 to receive Dapagliflozin Propanediol.  The primary outcome was a composite of a continual deterioration in the estimated Glomerular Filtration Rate [GFR] of at least 50 percent, end-stage kidney disease, or death due to cardiovascular or renal issues.   

The trial was stopped after a recommendation from the independent data monitoring committee due to the study’s efficacy. At a median of approximately 2.4 years, a primary outcome happened in 197 out of 2152 patients in the Dapagliflozin Propanediol group and 312 out of 2152 in the placebo group.  The hazard ratio for the composite of a continued decline in the estimated GFR of at least 50 percent, end-stage kidney disease, or death from renal causes was 0.56 (95 percent CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular effects or hospitalization due to heart failure was 0.71 (95 percent CI, 0.55 to 0.92; P=0.009).  Death in the Dapagliflozin Propanediol group was 101 participants (4.7 percent) and 146 (6.8 percent) in the placebo group.  The overall effects of Dapagliflozin Propanediol were seen in the patients with and without type 2 diabetes.   

The trial showed that regardless of whether the patients had type 2 diabetes or not, the chronic kidney disease risk of a continual decline in the estimated GFR of at least 50 percent, end-stage kidney disease, or death from renal or cardiovascular effects was significantly lower in the Dapagliflozin Propanediol group than the placebo group. Since, one-third of the patients did not have diabetes, this opened the opportunity for an SGLT2 inhibitor to be used in a new group of patients. The study also showed that patients with diabetes did see a benefit without experiencing severe ketoacidosis or hypoglycemia, a common complication for SGLT2 inhibitors.  The trial stopped early due to overwhelming efficacy, similar to the CREDENCE trial.   

Practice Pearls: 

  • Chronic kidney disease patients are at a higher risk of adverse kidney and cardiovascular outcomes.  
  • DAPA-CKD found that Dapagliflozin Propanediol caused a lower risk of the primary outcomes of estimated GFR of at least 50 percent, end-stage renal disease, or death from renal or cardiovascular effects.  
  • The estimated glomerular filtration rate has to be between 25-75 milliliters per minute, and the urinary albumin to creatine ratio of 200 to 5000, to be a candidate for Dapagliflozin Propanediol.   

 

“FARXIGA® (Dapagliflozin Propanediol ).” Treatment for Type 2 Diabetes & Heart Failure | FARXIGA® (Dapagliflozin Propanediol ), 2020, www.farxiga-hcp.com/?source=frx_n_h_1375 

Caffrey, Mary. DAPA-CKD: Dapagliflozin Drops Risk of Renal Decline or Kidney Failure Death 39%, Even Without Diabetes. European Society of Cardiology, 2020.  

Dapagliflozin Propanediol in Patients with Chronic Kidney Disease: NEJM. 2020,  

 

A’Kira Shavers, PharmD Candidate, South College School of Pharmacy