A Randomized Study of the Effects of Dapagliflozin+Saxagliptin in Addition to Metformin Versus Single Addition Saxagliptin or Dapagliflozin on Glucose Metabolism in Patients With DM2 Poorly Controlled With Metformin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Glucose Metabolism
研究概览
简要总结
A phase IV, randomized, double-blind, single center pilot study in subjects with type 2 diabetes poorly controlled with metformin therapy will be randomized to receive, on top of metformin: saxagliptin (5 mg/day) and dapagliflozin (10 mg/day) (Group 1);saxagliptin (5 mg/day) and placebo (Group 2); dapagliflozin (10 mg/day) and placebo (Group 3) for 4 weeks.
详细描述
Dapagliflozin (Forxiga) currently is approved for the treatment of T2DM (6). Dapagliflozin inhibits SGLT2, promote the excretion of 80-90 grams of glucose per day in the urine, and lower the plasma glucose concentration. This class of drugs has been shown to effectively reduce the HbA1c at all stages of T2DM and can be used in combination of all other anti-diabetic agents including insulin.
Saxagliptin is a highly potent DPP4 inhibitor.In patients with type 2 diabetes, administration of saxagliptin led to inhibition of DPP4 enzyme activity for a 24-hour period.After an oral glucose load,this DPP4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), decreased glucagon concentrations and increased glucose-dependent beta-cell responsiveness, which resulted in higher insulin and C-peptide concentrations.The rise in insulin from pancreatic beta-cells and the decrease in glucagon from pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.Saxagliptin improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.
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
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females
- •Age = 35-70 years
- •BMI ≤ 40 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months
- •Type 2 diabetes (HbA1c > 7 % and < 10 %)
- •Metformin on stable dose (at least 1500 mg/day) for at least 12 weeks before screening and at study initiation.
- •Subjects who are women of childbearing potential must agree to utilize a highly effective contraceptive measure throughout the course of the study.. 7.
- •Subjects are capable of giving informed consent
排除标准
- •Drugs known to affect glucose metabolism (other than metformin) for more than14 days during the 12 weeks before screening
- •Known Dapagliflozin and Saxagliptin Excipient Hypersensitivity
- •Type 1 Diabetes or History of Ketoacidosis
- •history of cancer of any type;
- •cerebrovascular or symptomatic peripheral vascular disease;
- •heart disease class III or IV NYHA;
- •Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m 2 or serum creatinine > 1.5mg/dL in men or >1.4mg/dL in women
- •Liver function enzymes higher more than two times the upper limit
- •Ongoing urinary tract infection
- •drug or alcohol abuse;
- •life expectancy <3 yrs
- •blood pressure >160/100 mmHg
- •Donation of blood to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 8 weeks prior to the enrollment visit and at least 8 weeks thereafter
- •Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study (estrogen and/or progesterone treatment)
- •Women who are pregnant or breastfeeding
- •Patient with a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient or interfere with trial procedures
研究组 & 干预措施
Dapagliflozin 10mg
Dapagliflozin inhibits SGLT2 promoting the excretion of glucose in the urine,and lowers the plasma glucose concentration. This class of drugs has been shown to effectively reduce the HbA1c at all stages of T2DM and can be used in combination of all other anti-diabetic agents including insulin.
干预措施: Dapagliflozin 10mg (Drug)
Saxagliptin 5mg
Saxagliptin is a DPP4 inhibitor.In patients with type 2 diabetes,administration of saxagliptin led to inhibition of DPP4 enzyme activity.After an oral glucose load,this DPP4 inhibition resulted in a increase in circulating levels of active incretin hormones include GLP-1 and GIP, decreased glucagon concentrations and increased glucose-dependent beta-cell responsiveness,which resulted in higher insulin and C-peptide concentrations.The rise in insulin from pancreatic beta-cells and the decrease in glucagon from pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.Saxagliptin improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.
干预措施: Dapagliflozin 10mg (Drug)
Saxagliptin 5mg
Saxagliptin is a DPP4 inhibitor.In patients with type 2 diabetes,administration of saxagliptin led to inhibition of DPP4 enzyme activity.After an oral glucose load,this DPP4 inhibition resulted in a increase in circulating levels of active incretin hormones include GLP-1 and GIP, decreased glucagon concentrations and increased glucose-dependent beta-cell responsiveness,which resulted in higher insulin and C-peptide concentrations.The rise in insulin from pancreatic beta-cells and the decrease in glucagon from pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.Saxagliptin improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.
干预措施: Saxagliptin 5mg (Drug)
Saxagliptin 5 mg + dapagliflozin 10 mg
Please see Arm 1 and 2
干预措施: Saxagliptin 5mg + Dapagliflozin 10 mg (Drug)
结局指标
主要结局
Glucose Metabolism
时间窗: from first day
To determine the effect of the combination of dapagliflozin (a SGLT2-inhibitor) and saxagliptin (a DPP-4 inhibitor) on pancreatic hormones secretion and endogenous glucose production in Type 2 diabetic subjects through comparison of the effects of co-administration of Saxagliptin and Dapagliflozin vs. Saxagliptin or Dapagliflozin alone.
次要结局
未报告次要终点
研究者
Prof. Stefano Del Prato
Clinical Resercher
University of Pisa