Efficacy and Mechanism of Dapagliflozin Combined With Insulin in the Treatment of Early Diabetic Nephropathy in Patients With Type 1 Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- estimated Glomerular Filtration Rate
研究概览
简要总结
Diabetic kidney disease (DKD) is a leading cause of chronic and end-stage kidney disease, affecting 25-40% of type 1 diabetes (T1D) patients and 5-40% of type 2 diabetes (T2D) patients. Despite standard treatments like ACE inhibitors and ARBs, many patients continue to develop DKD, indicating a need for better kidney protection. This study aims to evaluate the efficacy and safety of dapagliflozin combined with insulin in early DKD patients with T1DM, using ACEi/ARB as standard treatment, to provide new insights into kidney protection and support precision medicine goals.
详细描述
This is an open-label, randomized, parallel-group study to evaluate the effects of dapagliflozin on urinary albumin/creatinine ratio (UACR) in participants with early diabetic nephropathy and type 1 diabetes mellitus (T1DM). The primary objective is to assess the changes in UACR and estimated glomerular filtration rate (eGFR) before and after dapagliflozin treatment in these patients. Secondary objectives include observing blood glucose control, weight improvement, and safety evaluation after dapagliflozin treatment.
The study comprises three groups: dapagliflozin 10 mg, dapagliflozin 5 mg, and a standard treatment control, with a 1:1:1 allocation ratio. Participants meeting the inclusion criteria and not meeting any exclusion criteria will enter a 4-8 week lead-in period, during which they will receive the maximum tolerable dose of ACEI/ARB medications, maintain this treatment for at least 4 weeks, and optimize blood glucose control under the guidance of medical professionals while wearing continuous glucose monitoring devices. Starting from baseline, participants will receive either dapagliflozin 5 mg or 10 mg once daily for 24 weeks, while the control group will continue on the maximum tolerable dose of ACEI/ARB medications. Continuous glucose monitoring and regular ketone monitoring will be performed to prevent diabetic ketoacidosis. Follow-up visits will occur approximately 30 days after the last dose of study medication or upon study completion.
The primary efficacy indicators are the mean changes in UACR and eGFR from baseline to week 24. Secondary efficacy indicators include changes in 24-hour urine biochemistry, HbA1c, body weight, continuous glucose monitoring indices, and total daily insulin dose. Safety evaluation indicators include adverse events, serious adverse events, diabetic ketoacidosis, severe hypoglycemia, and urinary or genital infections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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
- •Age between 18 and 65 years;
- •Diagnosed with type 1 diabetes mellitus with a disease duration of more than 5 years;
- •Glycated hemoglobin (HbA1c) ≤ 7.5% at screening;
- •Diagnosed with diabetic nephropathy;
- •UACR between 30 and 300 and eGFR ≥ 60 ml/min/1.73 m².
排除标准
- •Other types of diabetes;
- •Use of any antidiabetic medications (excluding insulin) within 1 month prior to screening;
- •History of diabetic ketoacidosis within 3 months prior to screening, or a diagnosed episode of diabetic ketoacidosis within the past 1 month;
- •History of poor blood glucose control requiring hospitalization (due to hyperglycemia or hypoglycemia) within 1 month prior to screening;
- •Frequent severe hypoglycemia or unconscious hypoglycemia (more than once requiring medical intervention or emergency care) within 1 month prior to screening;
- •Use of SGLT2 inhibitors or other renal protective medications within 6 months prior to screening;
- •Women who are planning to become pregnant, pregnant, or breastfeeding;
- •Cardiovascular disease (within 6 months prior to screening);
- •Unstable/rapidly progressing renal disease (within 6 months prior to screening), or renal artery stenosis;
- •Major liver disease or malignant tumors (within 5 years prior to screening).
研究组 & 干预措施
Drug: Dapagliflozin 10 MG + ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment, dapagliflozin is administered at a dose of 10 mg once daily, without food restrictions, for a total treatment duration of 24 weeks.
干预措施: dapagliflozin (Drug)
Drug: Dapagliflozin 10 MG + ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment, dapagliflozin is administered at a dose of 10 mg once daily, without food restrictions, for a total treatment duration of 24 weeks.
干预措施: ACE inhibitor (Drug)
Drug: Dapagliflozin 5 MG + ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment, dapagliflozin is administered at a dose of 5 mg once daily, without food restrictions, for a total treatment duration of 24 weeks.
干预措施: dapagliflozin (Drug)
Drug: Dapagliflozin 5 MG + ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment, dapagliflozin is administered at a dose of 5 mg once daily, without food restrictions, for a total treatment duration of 24 weeks.
干预措施: ACE inhibitor (Drug)
Drug: ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment for a total treatment duration of 24 weeks.
干预措施: ACE inhibitor (Drug)
结局指标
主要结局
estimated Glomerular Filtration Rate
时间窗: From baseline to 24 weeks
Average change from baseline to 24 weeks after treatment
Urinary albumin-to-creatinine ratio
时间窗: From baseline to 24 weeks
Average change from baseline to 24 weeks after treatment
次要结局
- HbA1c(From baseline to 24 weeks)
- 24-hour urine biochemical quantification(From baseline to 24 weeks)
- Weight(From baseline to 24 weeks)
- Time in Range(From baseline to 24 weeks)
- Daily insulin dose(From baseline to 24 weeks)