A Multicenter, Register-based, Randomized, Controlled Trial Comparing Dapagliflozin With Metformin Treatment in Early Stage Type 2 Diabetes Patients by Assessing Mortality and Macro- and Microvascular Complications
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 2,067
- 试验地点
- 1
- 主要终点
- Time to first occurence of a confirmed composite endpoint of death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer.
研究概览
简要总结
A real-world, nationwide, register-based, randomised trial (RRCT) comparing SGLT2 inhibitors with metformin as standard treatment in early typ 2 diabetes. An open-label trial addressing efficacy with respect to clinically important macro- and microvascular events.
详细描述
2067 type 2 diabetes (T2D) patients on monotherapy or drug naive. Randomization 1:1, metformin, dosing according to treatment guidelines or SGLT2 inhibitor, dapagliflozin 10 mg od.
844 events estimated for study completion (90% power to detect hazard ratio (HR) <0.8 for dapagliflozin vs metformin ) Endpoint collection during study duration (about 4 years) from national health care registers: Patient, Prescribed drugs, Cause of death and Population registers; National diabetes register (NDR) Primary analysis according to insulin tolerance test (ITT)
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
- Single (Outcomes Assessor)
盲法说明
Treatment is blinded to outcome analysis team, until after database lock
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ≥18 years old
- •T2D (according to World Health Organization (WHO) criteria) of less than 4 years duration
- •BMI 18.5-45 kg/m2
- •Drug naïve or oral monotherapy with glucose-lowering drug.
- •Accepting NDR participation and other register data collection.
排除标准
- •Known or suspected other form of diabetes than type 2
- •Ongoing or more than >4 weeks in total of any previous treatment with: insulin, GLP-1 receptor agonists, SGLT2 inhibitors or combination of any diabetes medications
- •Medical need to start or intensify any specific GLD treatment, e.g. insulin due to marked hyperglycemia
- •HbA1c >70 mmol/mol for patients on monotherapy, >80 in drug naïve
- •Contraindication to either metformin or dapagliflozin, or any unacceptable risk with either treatment as assessed by the investigator
- •History or signs of established cardiovascular disease: diagnosis of myocardial infarction, angina pectoris, heart failure, stroke, lower extremity arterial disease, any limb amputation (except due to trauma or malignancy)
- •Any serious illness or other condition with short life expectancy (<4 yr)
- •Renal impairment (eGFR <60 ml/min/1,73m2)
- •Any condition, as judged by the investigator, that suggests that the patient will be non-compliant or otherwise unsuitable to study medication or study participation
- •Pregnancy or breastfeeding, women of childbearing potential (WOCBP; including perimenopausal women who have had a menstrual period within 1 year) without adequate anticonception during any part of the study period
- •Involvement in the planning and/or conduct of the study
- •Ongoing participation in another clinical trial.
研究组 & 干预措施
Metformin
Metformin 1000-3000 mg per day according to clinical guidelines. Split into 2-3 doses per day.
干预措施: Metformin (Drug)
Dapagliflozin
Dapagliflozin 10 mg once daily
干预措施: Dapagliflozin 10 MG (Drug)
结局指标
主要结局
Time to first occurence of a confirmed composite endpoint of death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer.
时间窗: Time to first event during study period (for each patient 24-48 months, mean 36 months )
A confirmed composite endpoint includes death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer (ICD10 diagnosis codes)
次要结局
- Death(Time to event during study period (for each patient 24-48 months, mean 36 months))
- Microvascular events, first of; occurrence or progression of retinopathy, nephropathy, diabetic foot lesions(Time to first event during study period (for each patient 24-48 months, mean 36 months ))
- Health-related quality of life(Assessment at baseline, 12, 24 months)
- Health-related quality of life with respect to diabetes treatment satisfaction.(Assessment at baseline, 12, 24 months)
- Ordinal analysis of components of primary endpoint (see above)(Events of any of above having occurred during 48 months following randomization.)
- Time to first occurence of a confirmed composite endpoint of non-fatal myocardial infarction, stroke, heart failure, unstable angina or cardiovascular death.(Time to first event during study period (for each patient 24-48 months, mean 36 months ))
- Change in glycemic control(Change during study period, at 12, 24, 36 and 48 months)
- Change in HDL-cholesterol(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)
- Change in total cholesterol(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)
- Change in blood pressure(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)
- Treatment failure, defined as add-on or switch to another glucose-lowering drug(Time to first event during study period (for each patient 24-48 months, mean 36 months ))
- Change in triglycerides(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)
- Health care costs(Accumulated health care costs during study period (for each patient 24-48 months, mean 36 months ))
- Change in LDL-cholesterol(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)
- Change in BMI(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)
- Time to first occurence of a confirmed composite endpoint of death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer (ICD10 diagnosis codes) or initiation of insulin treatment.(Time to first event during study period (for each patient 24-48 months, mean 36 months ))
- Time to first occurence of a confirmed composite endpoint of heart failure or cardiovascular death.(Time to first event during study period (for each patient 24-48 months, mean 36 months ))
- Need for insulin treatment(Time to first event during study period (for each patient 24-48 months, mean 36 months ))
- Change in albuminuria(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)
- Change in body weight(Change during study period; assessment at baseline, 12, 24, 36 and 48 months)