The effect of empagliflozin on inflammation in patients with overweight or obesity and risk of heart failure: a substudy from the Empire Prevent Metabolic trial.

Abstract

Background: Obesity increases the risk of heart failure (HF), potentially through low-grade inflammatory processes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been suggested to attenuate inflammation, although data in patients without diabetes and HF are lacking. Moreover, it is unknown whether SGLT2 inhibitors affect adipose tissue dysfunction. We aimed to investigate the effect of the SGLT2 inhibitor empagliflozin on systemic inflammation, uric acid, and adipose tissue dysfunction in high-risk patients with overweight or obesity.

Methods: Pre-defined secondary analysis of the Empire Prevent Metabolic trial. Outpatients with body mass index (BMI) > 28 kg/m² and risk factors for HF, excluding diabetes, were randomised to 180 days treatment with empagliflozin 10 mg or placebo. Patients completed blood sampling and subcutaneous abdominal adipose tissue biopsies at baseline and follow-up. Pre-defined endpoints were the baseline-adjusted estimated treatment differences (ETD) or ratios (ETR) for interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), and uric acid. Furthermore, we explored gene expression changes in selected markers of adipose tissue dysfunction, including inflammation.

Results: We randomised 92 patients (empagliflozin: 44, placebo: 48). Median age was 68 years, median BMI was 31.6 kg/m², while 21 (23%) and 54 (59%) patients presented with IL-6 > 7 pg/ml and hsCRP of at least 3 mg/l, respectively. Empagliflozin did not affect IL-6 (ETR: 1.03, 95% CI 0.82-1.30, p = 0.78) or hsCRP (ETR: 1.15, 95% CI 0.87-1.51, p = 0.33) compared to placebo. Meanwhile, uric acid decreased (ETD: - 0.06 mmol/l, 95% CI - 0.08 to - 0.04, p < 0.0001), whereas no changes in adipose tissue gene expression were observed.

Conclusions: In this study, empagliflozin did not demonstrate anti-inflammatory effects but yielded possibly meaningful uricosuric effects in non-diabetic patients with overweight or obesity. Moreover, adipose tissue dysfunction remained unaltered. Trial registration clinicaltrials.gov NCT05042973.