Effect of Linagliptin + Metformin vs Metformin Alone on the Role of Pancreatic Islet Function, Insulin Resistance and Markers of Cardiovascular Risk in Patients With Prediabetes: Randomized Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- Change from basal fasting and post2h OGTT glucose levels at 12 and 24 months
研究概览
简要总结
Type 2 diabetes is a worldwide epidemic disease, and preventive strategies are needed to face this health problem. The goal of this clinical trial is to evaluate the effect of linagliptin + metformin vs metformin alone on physiopathological parameters, such as glucose metabolism, insulin resistance, insulin secretion and pancreatic beta cell function in patients with impaired fasting glucose plus impaired glucose tolerance, during 24 months.
详细描述
The main goal of this clinical trial is to compare the effect of two different treatments during 24 months:
- Lifestyle modification program + metformin 850mg twice daily
- Lifestyle modification program + linagliptin (2.5mg) and metformin (850mg) twice daily
on the following parameters, after 24 months of treatment:
- Glucose metabolism, evaluated by the oral glucose tolerance
- Insulin resistance, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients
- Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients
- Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients
- Systemic inflammation and cardiovascular risk factors, evaluated by cytokines interlelukin-6 (IL6), C-reactive protein (PCR), and measurement of the intima media thickness by ultrasound.
All the patients will have a basal evaluation with an oral glucose tolerance test, lipid profile, body composition, and IMT measurement by ultrasonography; and 10 % will be invited for the hyperglycemic clamp. After the basal evaluation, if the patients result with IMPAIRED GLUCOSE TOLERANCE and have at least 2 risk factors, they will be invited to the intervention phase where they will be randomized to one of the two treatment groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with prediabetes, defined for the existence impaired glucose tolerance (Glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance test (OGTT) ) with or without impaired fasting glucose (Fasting glucose between 100 and 125 mg/dL)
- •Patients who accept to participate in the study and sign the informed consent letter.
排除标准
- •Patients with diagnosed Type 2 Diabetes Mellitus previously or detected during the OGTT
- •Patients in actual treatment or during the last 3 months with metformin, pioglitazone or another antidiabetic drug, including insulin.
- •Serum creatinine > 1.6 mg/dL
- •Hypertriglyceridemia very high (>500 mg/dL)
- •Pregnant women
- •Altered arterial hypertension (Systolic > 180 mmHg or Diastolic >105 mmHg)
- •Excessive alcohol intake, acute or chronic
- •Medications or medical conditions that affect glucose homeostasis (thiazides, beta blockers, glucocorticoids for systemic use, weight-reducing drugs or anorexigenics, Cushing's syndrome, Thyrotoxicosis.
研究组 & 干预措施
Linagliptin + Metformin plus lifestyle
Patients are randomized to receive for 24 months Linagliptin 2.5mg + metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.
干预措施: Linagliptin + metformin (Combination Product)
Metformin plus lifestyle
Patients are randomized to receive for 24 months Metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.
干预措施: Metformin (Drug)
结局指标
主要结局
Change from basal fasting and post2h OGTT glucose levels at 12 and 24 months
时间窗: 12 and 24 months
Fasting and post-2h OGTT glucose values (mg/dl)
次要结局
- Change from basal pancreatic beta cell function at 12 and 24 months(12 and 24 months)
- Incidence of type 2 diabetes(24 months)
- Change from basal insulin sensitivity at 12 and 24 months(12 and 24 months)
- Change from basal Weight at 12 and 24 months(12 and 24 months)
研究者
Rodolfo Guardado Mendoza
MDPhD
Universidad de Guanajuato