Empagliflozin Treatment in HFrEF With Comorbid Diabetes/Prediabetes

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Patients with HFrEF who were diabetic or prediabetic had reduced left ventricular volumes following therapy with empagliflozin.

Patients with heart failure with reduced ejection fraction (HFrEF) who were diabetic or prediabetic had reduced left ventricular (LV) volumes following therapy with empagliflozin, according to study results published in Circulation.

In this multicenter randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT03485092), 105 patients (mean age, 68.7±11.1 years; 73.3% men) with HFrEF and type 2 diabetes or prediabetes were recruited between 2018 and 2020 at 15 hospitals in Scotland. Patients were randomly assigned at a 1:1 ratio to receive empagliflozin (10 mg daily; n=52) or placebo (n=53) for 36 weeks. Patients were assessed during 6 visits during which they underwent cardiovascular magnetic resonance imaging, standard laboratory analyses, and were examined for cardiovascular health.

In this cohort, 77.1% of participants had New York Heart Association (NYHA) functional class II, 49.5% had been previously hospitalized for HF, and 78.1% had type 2 diabetes mellitus.

At baseline, average LV end-systolic volume index (LVESVi) was 80.8±37.2 ml/m2 and 76.7±29.3 mL/m2 among patients receiving empagliflozin and placebo, respectively. At 36 weeks, LVESVi was reduced by 7.9±11.8 mL/m2 in the empagliflozin group compared with a 1.5 mL/m2 reduction in the placebo group (adjusted between-group difference, -6.0; 95% CI, -10.8 to -1.2 mL/m2; P =.015).

The mean reduction in  LV end-diastolic volume index was greater in the empagliflozin vs placebo group (empagliflozin: baseline, 114.7±37.0 mL/m2; week 36, 105.7±37.6 mL/m2; placebo: baseline, 111.4±29.2 mL/m2; week 36, 110.9±28.3 mL/m2; adjusted between-group difference, -8.2; 95% CI, -13.7 to -2.6 mL/m2; P =.004).

No difference for LV global longitudinal strain was observed (adjusted between-group difference, 0.35%; 95% CI, -0.25% to 0.95%; P =.25).

Patients receiving empagliflozin vs placebo had greater reductions in: uric acid (adjusted between-group difference, -66.2 umol/L; 95% CI, -91.9 to -40.5 umol/L; P <.0001), hematocrit (adjusted between-group difference, 0.027 L/L; 95% CI, 0.015-0.038 L/L; P <.0001), galectin-3 (adjusted between-group difference, 1.94 ng/mL; 95% CI, 0.41-3.47 ng/mL; P =.013), and N-terminal pro-B-type natriuretic peptide (adjusted between-group difference, -28%; 95% CI, -47% to -2%; P =.038).

Safety outcomes were comparable between the 2 groups, however, deaths occurred in 2 participants treated with empagliflozin (due to pancreatic cancer and cardiogenic shock).

These findings may not be generalizable to a more frail population, as patients with atrial fibrillation, cardiac devices, or NYHA functional class IV were excluded from this study.

“[T]reatment with the SGLT2 inhibitor empagliflozin led to favorable reverse LV remodeling in patients with HFrEF and type 2 diabetes or prediabetes,” concluded the study authors. “This finding may, at least in part, explain the beneficial effect of SGLT2 inhibitors on clinical outcomes in HFrEF.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Lee M M Y, Brooksbank K J M, Wetherall K, et al. Effect of Empagliflozin on Left Ventricular Volumes in Patients with Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF). [published online November 13, 2020] Circulation. doi:10.1161/CIRCULATIONAHA.120.052186