SGLT2 Inhibitors Associated With High Hemoglobin Level, Low Prevalence of Anemia

Data from multiple short-term clinical trials reported increased hemoglobin levels after sodium-glucose cotransporter 2 (SGLT2) inhibitor use in patients with diabetes, but it is still unknown if SGLT2 inhibitors improve anemia in clinical practice.

Thus, a recent study sought out the association between the use of SGLT2 inhibitors and hemoglobin levels of anemia in a cross-sectional study, as well as a case-control study among all diabetic patients in an outpatient setting.

Led by Miho Murashima, MD, PhD, Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, investigators observed the association of SGLT2 inhibitors with higher hemoglobin levels and lower prevalence of anemia in clinical practice.

Methods

Inclusion criteria for the retrospective observational study began with patients with diabetes who visited the outpatient clinic at the Department of Endocrinology and Diabetes or Department of Nephrology at Nagoya City University Hospital from January 2019 - August 2020.

The study defined diabetes as either taking glucose-lowering agents or having a hemoglobin A1c ≥6.5%. Additionally, exposures of interest were defined as the use of SGLT2 inhibitors, while the study noted that at the time of study, they were not approved for nondiabetic patients in Japan.

Then, outcomes were defined as the patient’s hemoglobin level or anemic status, defined as <120 g/L for men and <110 g/L for women or the use of erythropoiesis-stimulating agents (ESAs).

Investigators also noted that hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors were not approved for patients with non-dialysis-dependent chronic kidney disease (CKD) in Japan.

During the cross-sectional analyses, non-linear regression models were fitted with restricted cubic splines in order to investigate the association between hemoglobin level and estimated glomerular filtration (eGFR) for both users and non-users of SGLT2 inhibitors.

In the case-control study, cases and controls were matched 1:1 by age within 5 years, sex, and eGFR within 1 mL/min/1.73 m².

Findings

Out of a total of 5111 patients who visited the Department of Nephrology or Department of Endocrinology at Nagoya City University Hospital throughout the study period, 2063 patients were considered diabetic after exclusion of 158.

In those with diabetes, 723 patients were on an SGLT2 inhibitor and 581 had anemia, with the most commonly used SGLT2 inhibitor including canagliflozin followed by dapagliflozin and tofogliflozin.

Data show in the cross-sectional analysis, the hemoglobin level of SGLT2 inhibitor users were higher at an eGFR above >15 mL/min/1.73 m² compared to non-users. Additionally, the probability of anemia for SGLT2 inhibitor users was found to be lower at an eGFR above 30 mL/min/1.73 m².

Then, in the case-control study, 197 cases and controls were well-matched by age, sex, and eGFR. Murashima and colleagues observed the use of an SGLT2 inhibitor was associated with a significantly lower prevalence of anemia (OR, 0.35, 0.21 - 0.58) in univariate analysis.

In the propensity score-matched analysis, the adjusted mean differences (95% confidence intervals) in hemoglobin levels were 5.0 (1.0 - 8.0), 7.0 (3.0 - 10.0) and 7.0 (4.0 - 11.0) g/L at 3, 6 and 12 months, respectively.

At 6 months after initiation of SGLT2 inhibitors, the odds of increase in 6-month hemoglobin were similar across eGFR categories, except eGFR <15 mL/min/1.73 m².

Takeaways

“The use of SGLT2i was associated with higher hemoglobin levels and a lower prevalence of anemia in real-world clinical practice, including those with advanced CKD, active malignancy, or acute illness,” investigators wrote.

The study, “Sodium-​​glucose cotransporter 2 inhibitors and anemia among diabetic patients in real clinical practice,” was published in the Journal of Diabetes Investigation.