Save Those Kidney Beans: Nephro-Protective Effects of SGLT2 Inhibitors

By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS 

Volume3, Issue 1

“Pour some sugar on me”

SGLT2 inhibitors have morphed into somewhat of a pharmacologic panacea over the last half-decade. First, there was the serendipitous discovery of cardio-protective effects in patients with diabetes. Next, studies like DAPA-HF and EMPA-Reduced were conducted in a heart failure population and confirmed cardio- and nephro-protective effects in this vulnerable group. Numerous FDA approvals followed, first for cardio-protection in patients with diabetes (all three agents) and then to reduce the risk of death and hospitalization in patients with heart failure (dapagliflozin). On January 12, 2021, the FDA accepted a supplemental NDA for empagliflozen for similar heart failure indication. Then on April 30^th, the FDA granted a new approval for dapagliflozin specifically in patients with chronic kidney disease (CKD). In this week’s issue of Talking Therapeutics, we explore this new approval and what it means for CKD patients.

Point 1: DAPA tastes sweet victory in CKD

The specific language in the new labels states that dapagliflozin is now indicted to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk of progression. This label update was supported by results of the DAPA-CKD clinical trial, which evaluated the efficacy and safety of dapagliflozin compared to placebo on top of maximally tolerated ACEi/ARB therapy in patients with CKD (estimated glomerular filtration rate 25 to 75 mL/min and urinary-albumin-creatinine ratio 200 to 5000 mg/g). The primary endpoint was a composite of worsening renal function or renal or cardiovascular death and the trial was stopped early based on the recommendation of an independent data monitoring committee for overwhelming efficacy. Adverse event rates were low, which mirrors what was seen in prior dapaglifozin trials.

Point 2: There’s room for other SGLT2 inhibitors at the CKD table

Just this week, new data from the CREDENCE trial was published in Circulation, which showed that canagliflozin effectively lowered blood pressure and reduced rates of kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease in patients with diabetes and CKD.

Based on the accumulating clinical evidence for the beneficial effects of SGLT2 inhibitors in the management of CKD, both the 2021 American Diabetes Association Standards of Medical Care in Diabetes and the Kidney Disease Improving Global Outcomes (KDIGO) 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease advocate for the use of SGLT2 inhibitor therapy, in addition to metformin, in type 2 diabetes patients meeting eGFR criteria.

Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at New York- Presbyterian Hospital Columbia University Irving Medical Center.  He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, and India. Finally, Dr Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association.  

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