Journal Article

Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure

Tian, Rong, Wang, Dennis D., Isquith, Daniel, Sapp, Jamie, Maynard, Charles, Chu, Baocheng, Zhao, Xue-Qiao, Voronyuk, Anna, Tucker, Isabella, Ordovas, Karen, Huynh, Kim A., Balu, Niranjan, Naumova, Anna V., Kim, Francis

2024

Overview

Objective Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis. Research and design methods This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping. Results Between the baseline and 12-month time point, plasma IL-1B was reduced (− 1.8 pg/mL, P  = 0.003) while ketones were increased (0.26 mM, P  = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (− 158.9 pmole/min/10 6 cells, P  = 0.0497 vs. − 5.2 pmole/min/10 6 cells, P  = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups. Clinical Trial.gov Registration NCT03782259.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adults / Aged / Angiology / Anti-Inflammatory Agents - therapeutic use / Antidiabetics / Benzhydryl Compounds - adverse effects / Benzhydryl Compounds - therapeutic use / Biomarkers - blood / Cardiac fibrosis / Cardiology / Cardiomyopathy / Cardiovascular disease / Clinical outcomes / Clinical trials / CMRI / Congestive heart failure / Cytokines / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - diagnosis / Diabetes Mellitus, Type 2 - drug therapy / Diabetic Cardiomyopathies - blood / Diabetic Cardiomyopathies - diagnostic imaging / Diabetic Cardiomyopathies - drug therapy / Diabetic Cardiomyopathies - etiology / Diabetic Cardiomyopathies - prevention & control / Double-Blind Method / Female / Fibrosis / Glucose / Glucosides - adverse effects / Glucosides - therapeutic use / Health risks / Heart attacks / Heart failure / Humans / IL-1B / IL-1β / Inflammation / Inflammation - blood / Inflammation - diagnosis / Inflammation - drug therapy / Inflammation Mediators - blood / Interleukin 1 / Ketones / Magnetic resonance imaging / Male / Mapping / Medicine / Medicine & Public Health / Middle Aged / Myocardium - metabolism / Myocardium - pathology / Novel Cardioprotective Antidiabetic Medications / Oxygen consumption / PBMC respiration / Peripheral blood mononuclear cells / Placebo effect / Placebos / Plasma / Sodium-glucose cotransporter / Sodium-Glucose Transporter 2 Inhibitors - adverse effects / Sodium-Glucose Transporter 2 Inhibitors - therapeutic use / Time Factors / Treatment Outcome / Type 2 diabetes