Off taRget Effects of Linagliptin monothErapy on Arterial Stiffness in Early Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks
研究概览
简要总结
Diabetes is associated with an increased risk for developing premature macrovascular complications. The process of irreversible subclinical damage to the vasculature already starts during its preceding stages. Dipeptidyl peptidase (DPP)-4 inhibitors have been shown to attenuate vascular damage in preclinical studies. Off-target effects on adipose tissue inflammation, liver steatosis and atherosclerotic plaques have been extensively documented in animal studies.
Based on these considerations the investigators hypothesize that early therapy with the DPP4 inhibitor linagliptin in subjects with treatment naive type 2 diabetes will lead to beneficial effects on arterial stiffness as measured by pulse wave velocity.
详细描述
Patients with type 2 diabetes mellitus (T2DM) are at increased risk for developing premature macrovascular complications. The process of irreversible subclinical damage to the vasculature already starts during its preceding stages. At diagnosis, patients with T2DM already have evidence of subclinical vascular damage. Recent trials have shown no benefit of glucose lowering therapy when started later in the course of the disease, implicating that early interventions could be more effective in preventing macrovascular complications. Dipeptidyl peptidase (DPP)-4 inhibitors are oral antidiabetic drugs that increase the action of the naturally gut hormone glucagon-like peptide-1 (GLP-1), leading to improvement of postprandial insulin secretion, without hypoglycaemia or weight gain. DPP4 inhibitors improve beta-cell function and insulin resistance. More importantly, off-target effects on adipose tissue inflammation, liver steatosis and atherosclerotic plaques have been extensively documented in animal studies. Furthermore, DDP4 inhibitors improve the cardiovascular risk profile in small clinical studies. Based on these considerations the investigators hypothesize that early therapy with the DPP4 inhibitor linagliptin in subjects with type 2 diabetes will lead to beneficial effects on arterial stiffness, blood pressure and inflammatory markers independent of its effects on glycemic control.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women, age 30 to 70 years, AND
- •Treatment naïve type 2 diabetes, as defined as t
- •Fasting plasma glucose ≥ 7.0 mmol/l, OR
- •Random plasma glucose ≥ 11.1 mmol/l, OR
- •HbA1c ≥6,5%
- •Written informed consent
- •Assessable Pulse Wave Velocity measurement at screening
排除标准
- •Current or previous use of glycemic control medications
- •Type 1 diabetes
- •Gestational diabetes mellitus
- •Other specific types of diabetes due to other causes, e.g., genetic defects in β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation)
- •Uncontrolled hypertension, defined as systolic blood pressure >160 or a diastolic blood pressure >100 mmHg at screening visit
- •Severe dyslipidemia indicating primary dyslipidemia, defined as total cholesterol >8 mmol/l, triglycerides >10 mmol/l of high density lipoprotein cholesterol <0.6 mmol/l
- •Current use of weight loss medication or previous weight loss surgery
- •History of severe gastrointestinal disease
- •Clinical contraindications to DPP4-inhibitors
- •Previous cardiovascular disease, defined as stable coronary artery disease or acute coronary syndrome, stroke or transient ischemic attack, peripheral artery disease
- •Symptomatic heart failure, New York Heart Association (NYHA) class II-IV
- •Women who are currently pregnant,planning to become pregnant,breastfeeding women, or women with child bearing potential not using appropriate contraceptive measures
- •Clinically significant liver disease or hepatic function greater than 3 times upper limit of normal
- •Known impaired renal function or eGFR <30 ml/min/1.73m2
- •Patients who are mentally incompetent and cannot sign a Patient Informed Consent
- •Current active malignancy or in the previous 6 months
- •Documented HIV infection
- •Use of rifampicin
研究组 & 干预措施
Linagliptin
Linagliptin 5 mg/day + lifestyle advise
干预措施: Linagliptin (Drug)
Placebo
Matching placebo + lifestyle advise
干预措施: placebo (Drug)
结局指标
主要结局
change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks
时间窗: baseline, week 26
次要结局
- Secondary vascular study parameters(baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30))
- Subclinical vascular inflammation (FDG PET-CT)(26 weeks)
研究者
dr. DJ Mulder
MD, PhD
University Medical Center Groningen