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

• Published in: Cardiovascular diabetology Vol. 23; no. 1; pp. 197 - 9
• Main Authors: Wang, Dennis D., Naumova, Anna V., Isquith, Daniel, Sapp, Jamie, Huynh, Kim A., Tucker, Isabella, Balu, Niranjan, Voronyuk, Anna, Chu, Baocheng, Ordovas, Karen, Maynard, Charles, Tian, Rong, Zhao, Xue-Qiao, Kim, Francis
• Format: Journal Article
• Language: English
• Published: London BioMed Central 07.06.2024; BMC
• Subjects: 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; Type 2 diabetes; Cardiac fibrosis; PBMC respiration; Inflammation; IL-1B; SGLT2 inhibitor; CMRI
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-024-02294-z

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.