Empagliflozin Linked to Fluid Reduction in Type 2 Diabetes and CVD Patients

Atsushi Tanaka, MD, PhD

Empagliflozin has potential to reduce excess fluid in patients with type 2 diabetes and cardiovascular disease, according to data presented at the American Diabetes Association’s (ADA) 81st Scientific Sessions.

While the associations between the sodium-glucose cotransporter 2 (SGTL2) inhibitor and reduced risk of hospitalization for heart failure and cardiovascular death in these patients have been established, there is still little known about the mechanisms that mediate this relationship.

“Fluid regulation with SGLT2 inhibitor is a key action to prevent heart failure,” wrote the study investigators, led by Atsushi Tanaka, MD, PhD, of Sage University in Japan. “However, few evidence regarding early and serial effect of empagliflozin on such prognostic volume markers in patients with type 2 diabetes and established cardiovascular disease is currently available.”

The Study

The team conducted a post-analysis of the EMBLEM study, a multi-center, randomized, placebo-controlled, double-blind trial that evaluated the effects of empagliflozin treatment on vascular endothelial function in patients with both type 2 diabetes and cardiovascular disease.

Patients were randomized to either 10 mg empagliflozin once daily or placebo once daily for 24 weeks. Blood sampling was collected at baseline, weeks, 4, 12, and 24.

Tanaka and colleagues calculated estimated plasma volume (ePV) and estimated extracellular volume (eEV) at each visit in a subset of patients in the empagliflozin (n = 52) and placebo (n = 53) groups.

A longitudinal mixed-effects model for repeated measures was used to estimate mean change from baseline in ePV and eEV as well as 95% confidence intervals.

The Results

The mean ages of the empagliflozin and placebo subpopulations were 65 and 64 years old, respectively, and the majority in both groups were male (69.2% and 67.9%, respectively).

“Relative to placebo , empagliflozin reduced ePV by -2.23% (95% CI, -5.72 to 1.25) at week 4, -8.07% (95% CI, -12.76 to -3.37) at week 12, and -5.60% (95% CI, -9.87 to -1.32) at week 24,” the investigators reported.

“[Likewise, empagliflozin reduced] eEV by -70.3 mL (95% CI, -136.8 to -3.8) at week 4, -135.9 mL (95% CI, -209.6 to -62.3) at week 12, and -144.4 mL (95% CI, -226.3 to -62.4) at week 24,” they noted.

Even more, they found that the effects of the SGLT2 inhibitor on both ePV and eEV were largely consistent across patient characteristics.

Further, change in NT-proBNP concentrations was correlated with reductions in ePV (r = .351; P = .015) but not in eEV (r = .009; P = 0.953).

“Given the early cardiovascular benefits on empagliflozin seen in the EMPA-REG OUTCOME with a similar patient population, our findings suggest an important insight into key mechanisms underlying such clinical benefits of the drug,” Tanaka and colleagues concluded.

They indicated that further studies should be conducted to determine whether reductions in estimated fluid volume caused SGLT2 inhibition could predict longer-term outcomes in different types of patients.

The study, “Estimated Fluid Volume Status following Initiation of Empagliflozin in Patients with Type 2 Diabetes and Cardiovascular Disease,” was presented at ADA 2021.