Comparison of the Efficacy and Safety of Sodium-glucose Cotransporter 2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Obese Patients With Kidney Disease: a Single Center, Prospective, Exploratory Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Change of 24-hour urine protein quantification
研究概览
简要总结
The goal of this clinical trial is to exploring the changes in 24-hour urinary protein and renal function in obese patients with kidney disease after the application of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon like peptide-1 receptor agonists (GLP-1RA).
Eligible patients were randomly and non-blindly allocated to four groups in a 1:1:1:1 ratio.The first group is the optimized treatment group, and patients in this group maintain the maximum dose/maximum tolerated dose of RAS blocker therapy.
The second group is the optimized treatment + SGLT2i group. Participants in this group are titrated to the target dose (10 mg qd) in combination with dapagliflozin on the basis of optimized treatment.
The third group is the optimized treatment + GLP-1RA group. Participants in this group will be titrated to the target dose (1mg qw) in combination with semaglutide on the basis of optimized treatment.
The last group is the optimized treatment + SGLT2i + GLP-1RA treatment group, that is, based on the optimized treatment, combined with dapagliflozin titrated to the target dose (10 mg qd) and semaglutide titrated to the target dose (1 mg qw).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Agree to join this study and sign an informed consent form;
- •Age ≥ 18 years old and<75 years old;
- •BMI ≥ 25kg/m ² Or waist circumference ≥ 85cm (male)/≥ 80cm (female) or waist to hip ratio ≥ 0.9 (male)/≥ 0.85 (female);
- •Confirmed obesity related kidney disease through renal biopsy within six months;
- •Have received optimized treatment with RAS blockers and/or MRA for at least 3 months;
排除标准
- •Diagnosed as secondary obesity, such as hypothyroidism, Cushing's syndrome, polycystic ovary syndrome, etc;
- •Severe renal insufficiency (renal function eGFR<25 ml/min/1.73m2);
- •There is acute kidney injury; Defined as: (1) An increase in blood creatinine of ≥ 26.5 within 48 hours μ Mol/L; (2) Within 7 days, the increase in blood creatinine exceeds 1.5 times the baseline value or more; (3) Reduced urine output (<0.5 ml/kg/h) and lasting for more than 6 hours.
- •Symptoms of active reproductive and urinary system infections
- •Severe liver dysfunction (ALT/AST greater than 2.5 times the upper normal limit);
- •Severe cardiovascular and cerebrovascular diseases, rheumatic and immune diseases;
- •Serious metabolic diseases, such as diabetes ketoacidosis, hypertonic hyperglycemia, etc;
- •Late stage malignant tumors;
- •Have a known history of using drugs that affect glucose and lipid metabolism, such as glucocorticoids, antibiotics, anti anxiety or antidepressants, etc;
- •Severe bleeding tendency and inability to complete venous blood collection;
- •There are contraindications for MRI examination, such as patients with pacemakers, nerve stimulators, artificial metal heart valves, etc; Patients with claustrophobia; Epilepsy patients, etc.
- •Pregnant/lactating women;
研究组 & 干预措施
Basic treatment+GLP-1RA
On the basis of RAS inhibitors treatment, combined with semaglutide titrated to the target dose (1 mg qw).
干预措施: simagliptin：Forxiga®️ (Drug)
Basic treatment
RAS inhibitors（Losartan®️/Valsartan®️） : maintain the maximum dose/maximum tolerated dose.
干预措施: RAS inhibitors：Losartan®️/Valsartan®️ (Drug)
Basic treatment+SGLT2i
On the basis of RAS inhibitors treatment, combined with dapagliflozin and titrated to the target dose (10 mg qd).
干预措施: RAS inhibitors：Losartan®️/Valsartan®️ (Drug)
Basic treatment+SGLT2i
On the basis of RAS inhibitors treatment, combined with dapagliflozin and titrated to the target dose (10 mg qd).
干预措施: dapagliflozin：Forxiga®️ (Drug)
Basic treatment+GLP-1RA
On the basis of RAS inhibitors treatment, combined with semaglutide titrated to the target dose (1 mg qw).
干预措施: RAS inhibitors：Losartan®️/Valsartan®️ (Drug)
Basic treatment+SGLT2i+GLP-1RA
On the basis of RAS inhibitors treatment, combined with dapagliflozin titrated to the target dose (10 mg qd) and semaglutide titrated to the target dose (1 mg qw).
干预措施: RAS inhibitors：Losartan®️/Valsartan®️ (Drug)
Basic treatment+SGLT2i+GLP-1RA
On the basis of RAS inhibitors treatment, combined with dapagliflozin titrated to the target dose (10 mg qd) and semaglutide titrated to the target dose (1 mg qw).
干预措施: dapagliflozin：Forxiga®️ (Drug)
Basic treatment+SGLT2i+GLP-1RA
On the basis of RAS inhibitors treatment, combined with dapagliflozin titrated to the target dose (10 mg qd) and semaglutide titrated to the target dose (1 mg qw).
干预措施: simagliptin：Forxiga®️ (Drug)
结局指标
主要结局
Change of 24-hour urine protein quantification
时间窗: 4、12、24、36、48 WEEK
According to KDIGO 2021 glomerular disease management guidelines. ① Remission: proteinuria is reduced, and serum albumin is \>30g/L. Renal function is stable. Complete remission (CR): proteinuria is significantly reduced, 24HUTP\<0.3g/L, and serum albumin\>30g/L. Renal function is stable. Partial response (PR): proteinuria decreases, 24HUTP decreases \>50% from baseline and \>0.3g/L. Serum albumin\>30g/L. Renal function is stable. ② Invalid: proteinuria is not reduced compared with baseline, and serum albumin is \<30g/L. Renal function is stable or declining. ③Relapse: After achieving CR or PR, proteinuria increases (24-hour urine protein quantification ≥3.5g/d) and serum albumin decreases, \<30g/L. Renal function is stable or declining.
次要结局
- changes in fasting blood glucose(4、12、24、36、48 WEEK)
- Decline in glomerular filtration rate(4、12、24、36、48 WEEK)
- Changes in BMI(4、12、24、36、48 WEEK)