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

Cardiovasc Diabetol. 2023 Nov 28;22(1):330. doi: 10.1186/s12933-023-02027-8.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / adverse effects
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Erythropoiesis
  • Ferritins
  • Hemoglobins / metabolism
  • Hemoglobins / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Inflammation / diagnosis
  • Inflammation / drug therapy
  • Interleukin-6 / metabolism
  • Iron / metabolism
  • Iron / therapeutic use
  • Renal Insufficiency, Chronic* / diagnosis
  • Renal Insufficiency, Chronic* / drug therapy

Substances

  • saxagliptin
  • dapagliflozin
  • Iron
  • Interleukin-6
  • Hypoglycemic Agents
  • Benzhydryl Compounds
  • Hemoglobins
  • Ferritins

Associated data

  • ClinicalTrials.gov/NCT02547935