Prof. Heerspink

Diabetes Medication Dapagliflozin Evaluated for Effect on Anemia in Chronic Kidney Disease Interview with:
Prof. Heerspink
Prof. Hiddo Lambers Heerspink, PhD PHARMD

Department of Clinical Pharmacy and Pharmacology
University Medical Center Groningen
Groningen What is the background for this study? What is dapagliflozin primarily indicated for?


Response: Dapagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor. The multinational, double-blinded, randomized, placebo-controlled, DAPA-CKD trial demonstrated the kidney and cardiovascular benefits of dapagliflozin in 4304 patients with chronic kidney disease (CKD) with and without type 2 diabetes (T2D). Based on the results of this and other trials, current guidelines recommend use of SGLT2 inhibitors in patients with CKD, T2D, or heart failure.

Anemia is common among patients with CKD and is associated with worse clinical outcomes. Previous studies showed that SGLT2 inhibitors increase hemoglobin and hematocrit levels, but data are lacking in patients with CKD with and without T2D. In this post-hoc analysis of DAPA-CKD, we assessed the effect of dapagliflozin versus placebo on the correction and prevention of anemia in this population. What are the main findings?

Response: Relative to placebo, 10 mg dapagliflozin once daily increased hematocrit levels by 2.3 percentage points. Dapagliflozin also increased by 129% the chances of anemia correction among 1716 (40.0%) participants with anemia at baseline (defined as hematocrit <39% in men and <36% in women) and reduced by 61% the risk of anemia incident in those without anemia at baseline. Dapagliflozin also reduced by 43% the risk of anemia-related adverse events reported by the trial’s investigators. These beneficial effects of dapagliflozin on anemia-related outcomes were consistent in patients with and without T2D. What should readers take away from your report?

Response: Dapagliflozin prevented and corrected anemia more frequently than placebo in patients with CKD with and without T2D. These benefits are added to other favorable effects of dapagliflozin in this population, including lowering the risks of kidney function loss, albuminuria progression, hospitalizations for heart failure or due to other causes, and mortality. What recommendations do you have for future research as a results of this study?

Response: First, what are the mechanism(s) underlying the effect of dapagliflozin on anemia correction and prevention? Possible explanations may include increased erythropoietin synthesis, modifications of iron metabolism, and mitigation of inflammation.

Second, what are the relationships between dapagliflozin effects on anemia parameters with its other benefits?

Thirdly, are the benefits of dapagliflozin on anemia parameters translated to the real world settings?

Disclosures: HJLH is consultant for AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Gilead, Janssen, Merck, Mundi Pharma, Mitsubishi Tanabe, Novo Nordisk, and Retrophin. He has received research support from Abbvie, AstraZeneca, Boehringer Ingelheim, and Janssen.


Dapagliflozin and Anemia in Patients with Chronic Kidney Disease Akihiko Koshino, M.D.,1,2,* Meir Schechter, M.D.,1,3,4,* Glenn M. Chertow, M.D.,5 Priya Vart, Ph.D.,1 Niels Jongs, Ph.D.,1 Robert D. Toto, M.D.,6 Peter Rossing, M.D.,7,8 Ricardo Correa-Rotter, M.D.,9 John J.V. McMurray, M.D.,10 Jose Luis Gorriz, M.D.,  11 Rey Isidto, M.D.,12 Naoki Kashihara, Ph.D.,13 Anna Maria Langkilde, M.D.,14 David C. Wheeler, M.D.,15 and Hiddo J.L. Heerspink, Ph.D.1,16
Published May 19, 2023 DOI: 10.1056/EVIDoa2300049 NEJM Evid 2023; 2 (6)

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Last Updated on May 30, 2023 by Marie Benz