SGLT2 Inhibitors on Coronary Atherosclerosis Progression Via Perivascular Adipose Tissue in Diabetes

Randomization and blinding: Eligible participants will be randomly assigned in a 1:1 ratio to either the dapagliflozin group or the standard care control group using a centralized, computer-generated randomization sequence. This is an open-label trial; however, all outcome assessments will be performed by core laboratories blinded to treatment allocation. Imaging analyses for plaque volume, hemodynamic parameters, and perivascular adipose tissue metrics will be conducted by investigators masked to group assignment.

Intervention: Participants in the intervention group receive dapagliflozin 10 mg once daily in addition to their standard diabetes and cardiovascular care. Participants in the control group receive standard glycemic management according to current clinical guidelines, with the exclusion of SGLT2 inhibitors, GLP-1 receptor agonists, or DPP-4 inhibitors. The total study duration is 18 months.

Study procedures: At baseline, participants will undergo coronary computed tomography angiography (CCTA) using a standardized protocol. Blood samples will be collected for lipid panels and inflammatory markers. Quality of life will be assessed using the Seattle Angina Questionnaire (SAQ-7). Follow-up visits are scheduled at 6, 12, and 18 months. At each visit, adverse events, concomitant medications, and medication adherence will be recorded. The 18-month visit will include a repeat CCTA and blood sampling.

Imaging core laboratory: All CCTA images will be transferred to an independent core laboratory for quantitative analysis. Plaque volume and composition will be assessed using semi-automated software. CT-derived fractional flow reserve (CT-FFR) will be computed using a dedicated algorithm. Wall shear stress (WSS) will be derived from computational fluid dynamics. Perivascular adipose tissue parameters, including fat attenuation index (FAI) and fat volume, will be measured using a validated software tool.

Data and safety monitoring: An independent Data and Safety Monitoring Board (DSMB) will review unblinded safety data every 6 months. The DSMB will monitor for serious adverse events, including volume depletion, genital infections, hypoglycemia, diabetic ketoacidosis, and acute kidney injury. Protocol-defined stopping rules include a significant increase in any of these events in the intervention arm.

• Change in the Coronary Perivascular Fat Radiomics Score (FRS) from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in CT-derived fractional flow reserve (CT-FFR) from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in Fat Attenuation Index （FAI）from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in the Degree of Coronary Artery Stenosis from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in C-reactive protein (CRP) from baseline to 18 months [Срок оценки: Baseline to 18 months]
• Change in Quality of Life Score as Assessed by the Seattle Angina Questionnaire (SAQ-7) from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Occurrence of Major Adverse Cardiovascular Events (MACE) from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in Self-Rating Anxiety Scale（SAS） Score from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in Hamilton Anxiety Scale (HAMA) Score from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in wall shear stress (WSS) from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in Pericoronary Adipose Tissue Volume from Baseline to 18 Months [Срок оценки: Baseline to 18 months]
• Change in lipoprotein(a) (Lp(a)) from baseline to 18 months [Срок оценки: Baseline to 18 months]