Effect of Dapagliflozin on Cardio-Metabolic Risk Factors in Patients With Type-2 Diabetes
试验速览
- 阶段
- 4 期
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Subclinical atherosclerosis
研究概览
简要总结
Dapagliflozin is a member of the sodium-glucose cotransporter-2 (SGLT2) inhibitor class antidiabetes agents which produces significant and sustained reductions in glycemic parameters in patients with type 2 diabetes (T2DM). However, its non-glycemic effects are still largely unknown.
The investigators will evaluate for the first time the effect of dapagliflozin on multiple cardio-metabolic risk markers in one study. So far, no data on the effects of dapagliflozin as well as other SGLT-2 inhibitors on subclinical atherosclerosis, endothelial function, inflammatory markers, cytokines and atherogenic lipoproteins is available.
In addition, the investigators will examine microRNAs (miRNAs) implicated in the development and progression of atherosclerotic disease. Again, no data is currently available on dapaglifozin's as well as other SGLT-2 inhibitors' effects on miRNAs.
The results of this study will show for the first time the potential multiple, non-glycemic effects of dapagliflozin, reducing multiple cardio-metabolic risk markers, which will ultimately lead to decreased CV risk.
In addition, specific mechanisms of the dapagliflozin cardiovascular action will be investigated.
Finally, the results of this study may pave the way for personalized therapy (using the results on miRNAs).
详细描述
The investigators will perform an open label, two-arms, prospective intervention study using dapagliflozin+metformin vs. metformin alone for a period of 6 months in patients with T2DM.
The research hypothesis is to assess whether dapagliflozin can improve cardio-metabolic outcome, reducing subclinical atherosclerosis, endothelial dysfunction and different cardio-metabolic markers (including inflammatory markers, cytokines, oxidative stress and atherogenic lipoproteins) in patients with T2DM.
The primary objective is to assess the effects of dapagliflozin on subclinical atherosclerosis, as assessed by carotid intima-media thickness (cIMT).
Primary endpoint: Reduction in cIMT.
The secondary objective is to assess the effects of dapagliflozin on glycemic parameters (fasting plasma glucose (FPG), HbA1c), endothelial dysfunction, oxidative stress, atherogenic lipoproteins, inflammatory markers, cytokines and microRNAs (miR-130a, miR-27b, miR-29b and miR-210).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •men and women with T2DM;
- •age >18;
- •BMI ≥20 kg/m^2;
- •HbA1c 7.0-9.0 %;
- •receiving metformin therapy at least 1500 mg/day for at least 8 weeks before screening;
- •plasma triglycerides <400 mg/dL, plasma LDL-cholesterol < 250 mg/dL;
- •stabile daily dose(s) of hypolipidemic drugs (statins, ezetimibe) for at least 7 weeks prior to the day of randomization;
- •adequately controlled blood pressure (≤140/90 mmHg) to be maintained during the study according to Standard of Care;
- •able to swallow whole tablets.
排除标准
- •pregnancy or willingness to became pregnant;
- •severe liver dysfunction (alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 3 times upper limit of normal);
- •renal failure with glomerular filtration rate (eGFR) <60 ml/min/1.73m^2;
- •major cardiovascular event (myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack) within 12 weeks before screening;
- •severe infections (such as HIV and HCV);
- •any malignancy within 5 years before screening.
研究组 & 干预措施
Dapagliflozin
Dapagliflozin (10mg daily) as add-on to metformin (stable doses ranging from 1500 to 3000 mg daily).
The total duration of treatment is 6 months.
干预措施: Dapagliflozin 10mg (Drug)
Metformin alone
Metformin alone (stable doses ranging from 1500 to 3000 mg daily).
The total duration of treatment is 6 months.
干预措施: Metformin (Drug)
结局指标
主要结局
Subclinical atherosclerosis
时间窗: Change from baseline to 6 months of the treatment
To assess the effects of dapagliflozin on subclinical atherosclerosis, as assessed by carotid intima-media thickness (cIMT).
次要结局
- Endothelial dysfunction(Change from baseline to 6 months of the treatment)
- microRNAs(Change from baseline to 6 months of the treatment)
- Atherogenic lipoproteins(Change from baseline to 6 months of the treatment)
- Oxidative stress(Change from baseline to 6 months of the treatment)
- Inflammatory markers(Change from baseline to 6 months of the treatment)
研究者
Manfredi Rizzo
Associate Professor
University of Palermo