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| Name | Class |
|---|---|
| Medical Research Agency, Poland | OTHER_GOV |
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The purpose of the study is to compare the anti-atherosclerotic efficacy of oral treatment with a GLP-1 analogue (semaglutide) or an SGLT-2 (so-called "flozin") inhibitor (dapagliflozin) versus routine treatment (metformin) in patients with pre-diabetes and diagnosed coronary artery disease at 24 months.
The diagnosis of coronary artery disease will be defined as the presence of coronary atherosclerosis confirmed by coronary artery computed tomography (coronary CT).
The study will evaluate the effect of treatment with flozin vs. semaglutide compared to treatment with metformin on the progression/regression of coronary atherosclerosis, change in plaque character, and control of cardiovascular risk factors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DAPAGLIFLOZIN | Experimental | Dapagliflozin + OMT & Lifestyle Intervention |
|
| SEMAGLUTIDE | Experimental | Semaglutide + OMT & Lifestyle Intervention |
|
| METFORMIN | Active Comparator | Metformin + OMT & Lifestyle Intervention |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Semaglutide 14 MG [Rybelsus] | Drug | Semaglutide 3 mg daily - up-titrated to 7 mg daily if well tolerated - up-titrated to 14 mg daily if well tolerated |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of the effect of GLP-1 analogue treatment on coronary artery disease progression AND Evaluation of the effect of flozin treatment on the progression of coronary artery disease (CO-PRIMARY ENDPOINTS) | Change in % volume of noncalcified atherosclerotic plaque in the coronary arteries assessed by coronary CT versus routine management (intention-to-treat) AND Change in % volume of noncalcified atherosclerotic plaque in the coronary arteries assessed by coronary CT versus routine management (intention-to-treat) | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of the effect of each of the tested drugs vs. control group on progression of coronary artery disease | % change in volume of noncalcified atherosclerotic plaque assessed by coronary CT (as treated) between baseline and end of study | 24 months |
| Comparison of the effect of semaglutide vs. flozin on coronary artery disease progression |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jan Henzel, MD, PhD | Contact | +48 22 343 43 42 | jhenzel@ikard.pl | |
| Kinga Kotlinska | Contact | +48 22 343 40 88 | kkotlinska@ikard.pl |
| Name | Affiliation | Role |
|---|---|---|
| Jan Henzel, MD, PhD | National Institute of Cardiology | Principal Investigator |
| Mariusz Kruk, MD, PhD | National Institute of Cardiology | Study Chair |
| Cezary Kępka, MD, PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institute of Cardiology, Department of Coronary Artery and Structural Heart Diseases | Recruiting | Warsaw | Poland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-22/diabetes-total-risk-benefit-of-sglt2-inhibitors-and-glp1-agonists#.ZC8_KhOdj2E.link |
| Label | URL |
|---|---|
| Study information in Polish | View source |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 6, 2024 |
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| Dapagliflozin (Forxiga) | Drug | Dapagliflozin 10 mg daily |
|
| Metformin | Drug | Metformin 500 mg daily (up-titrated to 1000 mg daily if indicated) |
|
| Optimal Medical Therapy (OMT) And Lifestyle Intervention | Behavioral |
|
|
% change in volume of noncalcified atherosclerotic plaque assessed by coronary CT (intention to treat/as treated) between baseline and end of study |
| 24 months |
| Evaluation of the effect of each study drug vs. control group/comparison of the effect of semaglutide vs. flozin on progression of coronary artery disease | % change in volume of the entire atherosclerotic plaque assessed by coronary CT) (intention to treat/as treated) between baseline and end of study | 24 months |
| Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on progression of coronary artery disease | % change in volume of individual components of atherosclerotic plaque assessed by coronary CT (intention to treat/as treated) between baseline and end of study | 24 months |
| Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on progression of coronary artery disease (plaque conversion) | Conversion of non-calcified plaque to calcified plaque assessed by coronary CT (intention to treat/as treated) between baseline and end of study | 24 months |
| Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on CV risk expressed as the dynamics of high-risk features | Change in the number of high-risk atherosclerotic lesions defined as the presence of at least 2 high risk features among:
| 24 months |
| Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on CV risk on pericoronary fat attenuation index | Change in the Pericoronary Fat Attenuation Index assessed by coronary TK (intention-to-treat/as treated) between baseline and end of study | 24 months |
| Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - body weight | Change in total body mass (expressed in kilograms) (intention-to-treat/as treated) between baseline and end of study | 24 months |
| Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - body mass index | Change in body mass index (BMI), calculated as following body mass index (BMI) = total body mass / (height)^2 and expressed in kg/m2 (intention-to-treat/as treated) between baseline and end of study | 24 months |
| Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - total body fat | Change in totabl body fat mass (expressed in kilograms) measured by bioimpedance analysis (intention-to-treat/as treated) between baseline and end of study | 24 months |
| Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - body cell mass | Change in Body Cell Mass (BCM) (expressed in kilograms) measured by bioimpedance analysis (intention-to-treat/as treated) between baseline and end of study | 24 months |
| Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - fat to mass ratio | Change in fat to mass ratio (FMR), calculated as following fat to mass ratoi (FMR) = total body fat (TBF) / skeletal muscle mass measured by bioimpedance analysis (intention-to-treat/as treated) between baseline and end of study | 24 months |
| Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - visceral fat area | Change in visceral fat area (expressed in cm2) measured by bioimpedance analysis (intention-to-treat/as treated) between baseline and end of study | 24 months |
| Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - waist-to-hip index | Change in waist-to-hip index (WHI) measured by bioimpedance analysis between baseline and end of study | 24 months |
| Evaluation of change in inflammatory parameters in patients treated with semaglutide vs. patients treated with flozin | Change in concentration of high-sensitivity C-reactive protein between baseline and end of the study | 24 months |
| Evaluation of change in lipid levels in patients treated with semaglutide vs. patients treated with flozin | Change in
| 24 months |
| Evaluation of change in the percentage of glycated hemoglobin (HbA1c) in patients treated with semaglutide vs. patients treated with flozin | Change in the percentage of glycated hemoglobin (HbA1c) between baseline and end of study | 24 months |
| Evaluation of change in the percentage of patients with normal blood pressure in patients treated with semaglutide vs. patients treated with flozin | Change in percentage of patients with normal blood pressure defined as systolic pressure <140 mmHg and diastolic pressure <90 mmHg between baseline and end of study | 24 months |
| Evaluation of change in the percentage of patients smoking tobacco or electronic cigarettes in patients treated with semaglutide vs. patients treated with flozin | Change in the percentage of patients smoking tobacco (cigarettes, pipe, cigar, tobacco heating products) or electronic cigarettes as defined by the study protocol between baseline and end of study | 24 months |
| Evaluation of compliance with physical activity recommendations in patients treated with semaglutide vs. patients treated with flozin | Change in
| 24 months |
| Evaluation of dietary compliance in patients treated with semaglutide vs. patients treated with flozin | Change in the Dietary Approaches to Stop Hypertension (DASH) Index between baseline and end of study. For each of the 8 DASH food groups, a score of 10 is assigned when the DASH recommendation is met, lower intakes are scored proportionately, and the 8 individual scores are summed to create the overall DASH adherence score, which could range from 0 to 80. The higher the score, the better the adherence. Reference Günther AL, Liese AD, Bell RA, et al. Association between the dietary approaches to hypertension diet and hypertension in youth with diabetes mellitus. Hypertension. 2009 Jan;53(1):6-12 | 24 months |
| Type 2 diabetes diagnosis | Number of patients diagnosed with of diabetes based on the criteria of the Polish Diabetes Association during the study | 24 months |
| Evaluation of the onset of heart failure requiring hospitalization | Number of patients hospitalized for heart failure during the study | 24 months |
| Number of unscheduled hospitalizations | Number of unscheduled hospitalizations during the study | 24 months |
| Number of major cardiovascular events and strokes (MACCE: death/myocardial infarction/revascularization/stroke) separately and combined | Number of cardiovascular events and strokes (MACCE: death/myocardial infarction/revascularization/stroke) during the study | 24 months |
| Homeostatic Model Change Assessment - Insulin Resistance (HOMA-IR) | Change in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR) between baseline and of study | 12 and 24 months |
| Evaluation of change in the concentration of selected oxidative stress markers - catalase | Change in plasma concentration of catalase between baseline and end of study | 12 months and 24 months |
| Evaluation of change in the concentration of selected oxidative stress markers - superoxide dismutase (SOD) | Change in plasma concentration of superoxide dismutase (SOD) between baseline and end of study | 12 months and 24 months |
| Evaluation of change in the concentration of selected oxidative stress markers - Oxygen Radical Absorbance Capacity (ORAC) | Change in concentration of Oxygen Radical Absorbance Capacity (ORAC) between baseline and end of study | 12 months and 24 months |
| Evaluation of change in the concentration of selected oxidative stress markers - total antioxidant capacity (TAC) | Change in concentration of total antioxidant capacity (TAC) between baseline and end of study | 12 months and 24 months |
| National Institute of Cardiology |
| Study Chair |
| Oct 5, 2025 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
| C529054 | dapagliflozin |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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