Comparison of the Efficacy and Safety of SGLT2i and GLP-1 Receptor Agonists in Obese Patients With Kidney Disease

NCT06344247 | Recruiting DMC

• 1 other identifier: IIT-2023-0253
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Obesity; Chronic Kidney Diseases

Keywords

Obesity; Chronic kidney disease; Sodium glucose cotransporter 2 inhibitors (SGLT2i); Glucagon like peptide-1 receptor agonists (GLP-1RA)

Outcome Measures

Primary Outcomes (1)

• Change of 24-hour urine protein quantification

  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.

  4、12、24、36、48 WEEK

Secondary Outcomes (3)

• Decline in glomerular filtration rate

  4、12、24、36、48 WEEK

• Changes in BMI

  4、12、24、36、48 WEEK

• changes in fasting blood glucose

  4、12、24、36、48 WEEK

Study Arms (4)

Basic treatment

EXPERIMENTAL

RAS inhibitors（Losartan®️/Valsartan®️） : maintain the maximum dose/maximum tolerated dose.

Drug: RAS inhibitors：Losartan®️/Valsartan®️

Basic treatment+SGLT2i

EXPERIMENTAL

On the basis of RAS inhibitors treatment, combined with dapagliflozin and titrated to the target dose (10 mg qd).

Drug: RAS inhibitors：Losartan®️/Valsartan®️; Drug: dapagliflozin：Forxiga®️

Basic treatment+GLP-1RA

EXPERIMENTAL

On the basis of RAS inhibitors treatment, combined with semaglutide titrated to the target dose (1 mg qw).

Drug: RAS inhibitors：Losartan®️/Valsartan®️; Drug: simagliptin：Forxiga®️

Basic treatment+SGLT2i+GLP-1RA

EXPERIMENTAL

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).

Drug: RAS inhibitors：Losartan®️/Valsartan®️; Drug: dapagliflozin：Forxiga®️; Drug: simagliptin：Forxiga®️

Interventions

RAS inhibitors：Losartan®️/Valsartan®️ DRUG

Losartan®️/Valsartan®️ : maintain the maximum dose/maximum tolerated dose.

Basic treatment; Basic treatment+GLP-1RA; Basic treatment+SGLT2i; Basic treatment+SGLT2i+GLP-1RA

dapagliflozin：Forxiga®️ DRUG

Forxiga®️ : titrated to the target dose (10 mg qd).

Basic treatment+SGLT2i; Basic treatment+SGLT2i+GLP-1RA

simagliptin：Forxiga®️ DRUG

Semaglutide®️ : titrated to the target dose (1 mg qw).

Also known as: Semaglutide®️

Basic treatment+GLP-1RA; Basic treatment+SGLT2i+GLP-1RA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Renji Hospital Affiliated to Shanghai JIAO TONG University school of medicine

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

MeSH Terms

Conditions

Obesity; Renal Insufficiency, Chronic

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Central Study Contacts

Qin Wang

CONTACT

+8613621964604; qinwang_1975@126.com

Wei Jin

CONTACT

+8615026696535; jinwei_xj@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2024
• First Posted: April 3, 2024
• Study Start: September 1, 2023
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 3, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)