Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients With Prediabetes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Fasting Glucose
研究概览
简要总结
Prediabetes is a term that refers to alterations in glucose homeostasis, including impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both, involving a higher risk of progression type 2 diabetes mellitus (T2DM).
Dapagliflozin is a selective and reversible inhibitor of sodium-glucose type 2 (SGLT-2) co-transporter, which reduces renal glucose reabsorption and promotes the glucose excretion through urine, so that the blood glucose is improved in patients with T2DM. Although this mechanism is independent of insulin, there are evidence of improved secretion and insulin sensitivity, so it is interesting to assess these effects in patients with prediabetes, as potential therapy for treating such disorders and prevent progression to T2DM.
The aim of this study is to evaluate the effect of Dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes.
The investigators hypothesis is that the administration of dapagliflozin improve insulin secretion and insulin sensitivity in patients with prediabetes.
详细描述
A randomized, double-blind, placebo-controlled clinical trial in 24 patients with a diagnosis of prediabetes in accordance with the American Diabetes Association (ADA) without treatment.
They will be assigned randomly two groups of 12 patients each to receive 10 mg of Dapagliflozin (Forxiga, Astra Zeneca) or placebo, one per day before breakfast during 12 weeks.
There will be calculated Area Under the Curve of glucose and insulin, total insulin secretion (Insulinogenic index), first-phase of insulin secretion (Stumvoll index) and insulin sensitivity (Matsuda index).
This protocol it's already approved by the local ethics committee and written informed consent it's going to be obtained from all volunteers.
Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p ≤0.05.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients both sexes
- •Age between 30 and 60 years
- •Diagnosis of prediabetes according ADA criteria (fasting blood glucose levels between 100-126 mg/dl; postprandial blood glucose levels after an oral glucose tolerance test with 75 of oral glucose between 140-199 mg/dl; or glycosylated hemoglobin between 5.7-6.4%)
- •Informed consent signed
排除标准
- •Women with confirmed or suspected pregnancy
- •Women under lactation and/or puerperium
- •Hypersensibility to ingredients of intervention
- •Physical impossibility for taking pills
- •Known uncontrolled renal, hepatic, heart or thyroid diseased
- •Diabetes diagnosis
- •Previous treatment for glucose
- •Body Mass Index ≥35 kg/m2
- •Triglycerides ≥500 mg/dL
- •Total cholesterol ≥240 mg/dL
- •Low density lipoprotein (c-LDL) ≥190 mg/dL
- •Blood Pressure ≥140/90 mmHg
研究组 & 干预措施
Dapagliflozin
Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks.
干预措施: Dapagliflozin (Drug)
Placebo
Placebo capsules, one per day before breakfast during 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Fasting Glucose
时间窗: Fasting Glucose levels at week 12
The fasting glucose levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12
Postprandial Glucose
时间窗: Postprandial Glucose levels at Week 12
Postprandial glucose will be evaluated after a oral glucose tolerance test with enzymatic/colorimetric techniques and the entered values reflect the insulin sensitivity at week 12
Total Insulin Secretion
时间窗: Total Insulin Secretion at Week 12
Total insulin secretion will be calculated with insulinogenic index and the entered values reflect the total insulin secretion at week 12. The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus. Total insulin secretion was calculated with the insulinogenic index (ΔABC insulin/ΔABC glucose), the entered values reflect the total insulin secretion
First Phase of Insulin Secretion
时间窗: First Phase of Insulin Secretion at Week 12
The first phase of insulin secretion will be calculated with Stumvoll index and the entered values reflect the frst phase of insulin secretion at week 12. Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. First phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'), the entered values reflect the first phase of insulin secretion
Insulin Sensitivity
时间窗: Insulin Sensitivity at Week 12
Insulin sensitivity will be calculated with Matsuda index and the entered values reflect the insulin sensitivity at week 12. Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. The entered values reflect the insulin sensitivity
Glycosylated Hemoglobin
时间窗: Glycosylated Hemoglobin at Week 12
Glycosylated hemoglobin will be evaluated by ELISA and the entered values reflect the glycosylated hemoglobin at week 12
次要结局
- Total Cholesterol(Total Cholesterol levels at Week 12)
- Body Weight(Body Weight at Week 12)
- Uric Acid(Uric Acid levels at Week 12)
- Systolic Blood Pressure(Systolic Blood Pressure at Week 12)
- Diastolic Blood Pressure(Diastolic Blood Pressure at Week 12)
- Body Mass Index(Body Mass Index at Week 12)
- Triglycerides(Triglycerides levels at Week 12)
- High Density Lipoprotein Cholesterol (HDL-c)(HDL-c levels at Week 12)
- Alanine Aminotransferase (ALT)(ALT levels at Week 12)
- Aspartate Aminotransferase (AST)(AST levels at Week 12)
- Creatinine(Creatinine levels at Week 12)
研究者
Manuel González Ortiz
Researcher Professor
University of Guadalajara