Dapagliflozin Receives FDA Approval for Treatment of Chronic Kidney Disease

Editor’s Note: This content was written by Amit Goyal, MD, a cardiology fellow at the Cleveland Clinic, and co-founder of CardioNerds. DocWire News has partnered with Dr. Goyal and his team of correspondents to bring you the latest data and perspective from the front lines of practice and academic medicine. Stay tuned!

On April 30^th, 2021, the U.S. Food and Drug Administration approved dapagliflozin, a sodium/glucose cotransporter 2 (SGLT2) inhibitor, for a third indication: to reduce the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease (CKD) who are at risk for disease progression.

Dapagliflozin was previously approved to improve glycemic control in adults with type 2 diabetes mellitus in 2014 and to reduce the risk of cardiovascular death and hospitalization for heart failure in 2020. The most recent approval of dapagliflozin to reduce the risk of progression of CKD is a landmark decision based on the results of the DAPA-CKD trial, a randomized, double-blind, placebo-controlled, multicenter clinical trial.

Dapagliflozin becomes 1st #SGLT2i in class to be triple indicated (#T2D #HF #CKD)@US_FDA update likely represents the largest expansion to an at-risk population, now approved down to eGFR 25 for organ protection.

Stay tuned: #TRANSLATEHF data on intersection of HF+CKD #ACC2021 pic.twitter.com/fXfimZuYW8

— Muthu Vaduganathan (@mvaduganathan) May 1, 2021

The trial randomized 4304 adults with CKD (eGFR of 25 to 75 ml/min/1.73m²) and albuminuria (urine albumin-to-creatinine ratio of 200-5000 mg/g) regardless of diabetes status to receive dapagliflozin (10 mg daily) or placebo. Over a median of 2.4 years, the primary endpoint (composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes) occurred in 9.2% of those in those receiving dapagliflozin compared to 14.5% in those receiving placebo, resulting in a 39% relative risk reduction (HR=0.61; 95% CI, 0.51 to 0.72; P<0.001). This means that only 19 patients with CKD at risk for progression need to be treated with dapagliflozin over this time period to prevent one primary outcome event. There were also significant reductions in several secondary outcomes, including in death from any cause. The impressive results prompted early termination of the trial.

Today, the FDA approved dapagliflozin to reduce the risk of kidney function decline, kidney failure, CV death and hospitalization for HF in adults with CKD who are at risk of disease progression.

FDA Approves Treatment for Chronic Kidney Disease https://t.co/4QlbwRzpUt

— Gregg Fonarow MD (@gcfmd) April 30, 2021

Importantly, efficacy in DAPA-HF was similar in patients with and without type 2 diabetes as with efficacy of dapagliflozin and empagliflozin in patients with heart failure with reduced ejection fraction in DAPA-HF and EMPEROR-Reduced trials, respectively. The staggering and consistent efficacy of SGLT2 inhibitors in reducing major adverse cardiovascular and kidney events across several trial in different populations has spurred intense curiosity about the mechanistic basis for these overwhelming results. Benefits include improvements in glycemic control, blood pressure, weight loss, fluid status, and more. One thing is clear: we must no longer consider these as solely diabetes drugs. As ongoing trials further clarify and emphasize the role of a growing list of SGLT2 inhibitors for an expanding list of indications, equitable access remains a challenge and will need to be addressed in collaboration with relevant stake holders.

References

• FDA Press Release (DAPA-CKD) – https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chronic-kidney-disease
• FDA Press Release (DAPA-HF) – https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-type-heart-failure
• NEJM 2020 (DAPA-CKD) – https://www.nejm.org/doi/full/10.1056/NEJMoa2024816
• NEJM 2020 (EMPEROR-REDUCED) – https://www.nejm.org/doi/10.1056/NEJMoa2022190?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmedJournal