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Randomized Controlled Trial
. 2023 Nov 28;22(1):330.
doi: 10.1186/s12933-023-02027-8.

Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial

Akihiko Koshino  1   2 , Brendon L Neuen  3 , Niels Jongs  1 , Carol Pollock  4   5 , Peter J Greasley  6 , Eva-Marie Andersson  6 , Ann Hammarstedt  6 , Cecilia Karlsson  6 , Anna Maria Langkilde  6 , Takashi Wada  2 , Hiddo J L Heerspink  7   8
Affiliations
Randomized Controlled Trial

Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial

Akihiko Koshino et al. Cardiovasc Diabetol. .

Abstract

Background: This post-hoc analysis of the DELIGHT trial assessed effects of the SGLT2 inhibitor dapagliflozin on iron metabolism and markers of inflammation.

Methods: Patients with type 2 diabetes and albuminuria were randomized to dapagliflozin, dapagliflozin and saxagliptin, or placebo. We measured hemoglobin, iron markers (serum iron, transferrin saturation, and ferritin), plasma erythropoietin, and inflammatory markers (urinary MCP-1 and urinary/serum IL-6) at baseline and week 24.

Results: 360/461 (78.1%) participants had available biosamples. Dapagliflozin and dapagliflozin-saxagliptin, compared to placebo, increased hemoglobin by 5.7 g/L (95%CI 4.0, 7.3; p < 0.001) and 4.4 g/L (2.7, 6.0; p < 0.001) and reduced ferritin by 18.6% (8.7, 27.5; p < 0.001) and 18.4% (8.7, 27.1; p < 0.001), respectively. Dapagliflozin reduced urinary MCP-1/Cr by 29.0% (14.6, 41.0; p < 0.001) and urinary IL-6/Cr by 26.6% (9.1, 40.7; p = 0.005) with no changes in other markers.

Conclusions: Dapagliflozin increased hemoglobin and reduced ferritin and urinary markers of inflammation, suggesting potentially important effects on iron metabolism and inflammation.

Trial registration: ClinicalTrials.gov NCT02547935.

Keywords: Anemia; Ferritin; Hematopoiesis; Interleukin-6; Iron metabolism; Monocyte chemoattractant protein-1; Sodium glucose co-transporter 2 inhibitors; Transferrin.

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Conflict of interest statement

A. Koshino, N. Jongs and T. Wada have no conflicts of interest.B.L. Neuen has received fees for advisory boards, scientific presentations, speaker fees, steering committee roles and travel support from the American Diabetes Association, AstraZeneca, Bayer, Boehringer and Ingelheim, Cambridge Healthcare Research, Janssen and Medscape, with all honoraria paid to his institution. C. Pollock has served on the steering committee for CREDENCE trial of canagliflozin (sponsored by Janssen Cilag) and is an advisory board member and speaker for Astra Zeneca, and a speaker for Eli Lilly and Boehringer Ingelheim. P.J. Greasley, E.-M. Anderson, A. Hammarstedt, C. Karlsson and A.M. Langkilde are employees and shareholder of AstraZeneca.H.J.L. Heerspink is supported by a VIDI (917.15.306) grant from the Netherlands Organisation for Scientific Research and has served as a consultant for AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Fresenius, Gilead, Janssen, Merck, Mundipharma, Mitsubishi Tanabe, and Retrophin; and has received grant support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen.

Figures

Fig. 1
Fig. 1
Changes in markers of hematopoiesis, iron metabolism and inflammation. Mean absolute changes in (A) hemoglobin and (B) hematocrit over time. Mean percentage changes in (C) serum iron, (D) transferrin, (E) TSAT, (F) ferritin, (G) erythropoietin, (H) urinary MCP-1/Cr, (J) urinary IL-6/Cr and (K) serum IL-6. Numbers across bars represent between group differences in change relative to placebo group. Cr, creatinine; MCP-1, monocyte chemoattractant protein; IL-6, interleukin-6; TSAT, transferrin saturation
See this image and copyright information in PMC

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