Effectiveness and Tolerability of Novel, Initial Triple Combination Therapy With Xigduo (Dapagliflozin Plus Metformin) and Saxagliptin vs. Conventional Stepwise add-on Therapy in Drug-naïve Patients With Type 2 Diabetes
试验速览
- 阶段
- 3 期
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks
研究概览
简要总结
In this study, the investigators will assess the efficacy and tolerability of a novel, initial triple combination therapy with metformin, saxaglipitin, and dapagliflozin, compared to conventional stepwise add-on therapy in drug-naïve patients with recently onset type 2 diabetes.
详细描述
ADA/EASD guideline recommends sequential treatment approach starting with metformin, and adding other classes of anti-diabetic medications if target HbA1c is not achieved. However, several clinical studies clearly showed that initial dual or triple combination therapy was more favorable in terms of glycemic control.
A DPP-4 inhibitor saxagliptin increases serum level of GLP-1, and potentiates its action of increasing glucose-dependent insulin secretion and lowering glucagon secretion. A SGLT-2 inhibitor dapagliflozin lowers hyperglycemia via blocking SGLT-2 to increase glucosuria, that is, in an insulin-independent manner. Therefore, the mechanism of action of these drugs are complimentary to that of metformin, and all of these have a low risk of hypoglycemia and weight gain.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Drug-naïve patients with type 2 diabetes by American Diabetes Association criteria
- •HbA1c ≥ 8%, < 10.5% at screening
- •Age ≥ 18 years, < 65 years
- •Body mass index (BMI) ≥ 23 kg/m2, < 35 kg/m2
- •Estimated GFR (eGFR) ≥ 60 ml/min/1.73m2
排除标准
- •Uncontrolled hyperglycemia > 270 mg/dl after an overnight fast
- •Diabetic ketoacidosis
- •Type 1 diabetes
- •Confirmed cardiovascular disease (acute coronary syndrome, stroke, or transient ischemic attack) within 3 months of screening
- •Congestive heart failure (New York Heart Association functional class IV)
- •severe hepatic dysfunction (serum levels of either AST, ALT, or alkaline phosphatase above 3 x upper limit of normal (ULN))
- •alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake
- •pregnant women, women with potential of pregnancy not using adequate contraception method as evaluated by the investigator, lactating women
- •use of systemic glucocorticoid
研究组 & 干预措施
Triple combination therapy group
Xigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks
干预措施: triple combination therapy (Drug)
Stepwise add-on therapy group
- Participants were started on metformin 1000mg once daily after screening & assignment
- At each visits, FPG and HbA1c are measured. Sequential add-on therapy regimen is described
干预措施: Stepwise add-on therapy (Drug)
结局指标
主要结局
Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks
时间窗: 104 weeks
次要结局
- Changes in fat and lean mass from baseline to at 104 weeks(104 weeks)
- ∙ Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 52 weeks(52 weeks)
- Proportion of patients who met HbA1c < 7.0% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks(104 weeks)
- Change in body HbA1c from baseline to week 104(104 weeks)
- Change in body weight from baseline to week 104(104 weeks)
- Change in systolic blood pressure from baseline to week 104(104 weeks)
研究者
Sin Gon Kim
Professor
Korea University Anam Hospital