Dapagliflozin effects on haematocrit, red blood cell count and reticulocytes in insulin-treated patients with type 2 diabetes

Abstract

Recent studies have shown that high-risk patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose cotransporter 2 (SGLT2) inhibitors have improved cardiovascular (CV) outcomes. In an exploratory analysis of data from the EMPA-REG study, elevations in haematocrit were shown to be strongly associated with beneficial CV effects. As insulin treatment has been shown to be antinatriuretic, with an associated increase in extracellular fluid volume, it is important to confirm whether haematocrit increase is maintained with concomitant insulin therapy. Here, we investigate the effect of the SGLT2 inhibitor dapagliflozin on haematocrit, red blood cell (RBC) counts and reticulocyte levels in high-risk patients with T2DM receiving insulin. A 24-week, double-blinded, randomised, placebo-controlled trial (ClinicalTrials.gov: NCT00673231) was reported previously with extension periods of 24 and 56 weeks (total of 104 weeks). Patients receiving insulin were randomised 1:1:1:1 to placebo or dapagliflozin at 2.5, 5 or 10 mg. Haematocrit, RBC and reticulocyte measurements were conducted during this study, and a longitudinal repeated-measures analysis was performed here to examine change from baseline during treatment. Dapagliflozin treatment in combination with insulin resulted in a dose-dependent increase in haematocrit levels and RBCs over a 104 week period. There was a short-term increase in reticulocyte levels at the start of treatment, which dropped to below baseline after 8 weeks. SGLT2 inhibition with dapagliflozin leads to a sustained increase in haematocrit in patients receiving chronic insulin treatment.

Conflict of interest statement

J.A. has received researching funding from AstraZeneca and honoraria for lecturing or consulting from AstraZeneca and Boehringer Ingelheim. M.M. received lecture fees from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD and serves on advisory boards for AstraZeneca, Novo Nordisk, Eli Lilly. S.M.S. received lecture fees from AstraZeneca and Boehringer Ingelheim and served on advisory boards for AstraZeneca and Boehringer Ingelheim. C.T. received lecture fees from and served on advisory boards for AstraZeneca, Lilly, MSD and Novo Nordisk. E.J. has received honoraria for lecturing and consulting from AstraZeneca. K.R. is an employee of AstraZeneca. M.F.S. is a former employee of AstraZeneca and current employee of Bayer Pharmaceuticals. J.X. & W.T. are employees and shareholders of AstraZeneca. A.L.B. received lecture fees from AstraZeneca and Boehringer Ingelheim and served on advisory boards for AstraZeneca and Boehringer Ingelheim.

Figures

Figure 1

Effect of dapagliflozin on haematocrit, red blood cell and reticulocyte counts. Adjusted mean change from baseline for (A) haematocrit, (B) red blood cell count and (C) reticulocyte count over 104 weeks, including follow-up visit. The vertical dotted line marks the short-term study period (12 weeks). Error bars show ± 95% CI. B, baseline; CI, confidence interval; DAPA, dapagliflozin; F, follow-up; INS, insulin; PLA, placebo.

Figure 1

Effect of dapagliflozin on haematocrit, red blood cell and reticulocyte counts. Adjusted mean change from baseline for (A) haematocrit, (B) red blood cell count and (C) reticulocyte count over 104 weeks, including follow-up visit. The vertical dotted line marks the short-term study period (12 weeks). Error bars show ± 95% CI. B, baseline; CI, confidence interval; DAPA, dapagliflozin; F, follow-up; INS, insulin; PLA, placebo.