Clinical, Morphometric and Biochemical Effects on Adiposopathy Associated With the Use of GLP-1RA in CKD

NCT ID: NCT07309094

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

250 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-09-15

Study Completion Date

2028-12-31

Brief Summary

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Chronic kidney disease (CKD) is the progressive damage to kidney function, associated with an increased risk of cardiovascular diseases, such as stroke or myocardial infarct, particularly in the most severe stages of CKD, in which the patient requires dialysis. Several risk factors are reported for CKD, such as diabetes mellitus, obesity and hypertension. One of the most increasingly recognized risk factors is the fat tissue malfunction, known as adiposopathy. The accumulation of fat tissue around the organs in conditions of obesity or diabetes accelerates the production of pro-inflammatory factors that may worsen the kidney and heart damage. New antidiabetic medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RA), have proven beneficial effects on the kidney and heart due to several mechanisms, including anti-inflammatory actions and a potential action on the fat tissue.

The aim of this study is to assess the link between adiposopathy and CKD, by investigating the changes in adiposopathy measures throughout treatment with GLP-1RA to a sample of patients with CKD.

Detailed Description

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Chronic kidney disease (CKD) is defined as an irreversible abnormality of kidney structure and/or function lasting for more than three months. CKD is a major global health burden, affecting over 10% of the worldwide population and representing a leading cause of morbidity and mortality. Its progression to end-stage kidney disease (ESKD) drastically increases cardiovascular risk and is associated with a five-year survival rate of only approximately 50%. The principal risk factors for CKD-hypertension, obesity and type 2 diabetes (T2DM) in particular-are intrinsically linked through the dysfunction of fat/adipose tissue (AT), also known as adiposopathy.

Adiposopathy is a key driver of cardiorenal risk in CKD. Evidence from bioimpedance, imaging techniques (CT, MRI), and molecular biology studies confirm that alterations in adipose tissue-including its quantity, distribution (e.g., perirenal, epicardial), radiodensity, and the secretion of pro-inflammatory adipokines-are powerful triggers of cardiorenal damage and mortality in these patients. This understanding frames obesity, T2DM, cardiovascular diseases (CVDs), and CKD as different manifestations of a shared spectrum, now termed adiposity-based chronic disease (ABCD), necessitating an "adipocentric" therapeutic approach.

One hallmark feature of adiposopathy is the reprogramming and increase in size of certain region-specific adipose tissue. Perivisceral adipose tissue plays a pivotal role in adiposity-based chronic diseases as it releases adipokines and cytokines that not only contribute to the systemic pro-inflammatory and oxidative stress processes but may also influence the function of the organs surrounded by this tissue.

GLP-1RA stimulates the receptor for glucagon-like peptide-1 (GLP-1), an incretin-like hormone released in the large intestine that reduces serum glucose concentrations by stimulating the glucose-dependent release of insulin, inhibiting the hypersecretion of glucagon (except in hypoglycemia periods) and promoting satiety. GLP-1RA reduced the incidence of cardiovascular death in patients with T2DM compared with placebo and decreased the incidence of major kidney events, also reducing the progression of kidney dysfunction and the risk of death. In animals, the observed morphological changes generated by GLP-1RA could be underlined by potential actions on adipose tissue remodeling, as these drugs upregulated the expression of AT-browning related genes in perivisceral white adipose tissue from murine models, although the transcriptomic effects from GLP-1RA on the adiposopathy process are still unknown.

Conditions

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Chronic Kidney Disease stage3 Chronic Kidney Disease stage4 Chronic Kidney Disease Stage 1 Chronic Kidney Disease Stage 2 Obesity Diabetes Mellitus, Type 2

Keywords

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chronic kidney disease type 2 diabetes mellitus GLP-1RA adiposopathy perivisceral adipose tissue perirenal adipose tissue inflammation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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GLP-1RA Cohort

Patients receiving GLP-1RA, mainly semaglutide: weekly administration, subcutaneous form, from 0.25mg (starting dose) to 1mg (maintenance dose) with monthly increase (0.25-0.5-1mg)

GLP-1 receptor agonist

Intervention Type DRUG

Semaglutide: weekly subcutaneous administration, starting dose 0.25mg, maintenance dose 1mg

SGLT2 inhibitor

Intervention Type DRUG

dapagliflozin: oral administration from 5 to 10mg/day

SGLT2i Cohort

There will also be another comparative group of patients under SGLT2i

GLP-1 receptor agonist

Intervention Type DRUG

Semaglutide: weekly subcutaneous administration, starting dose 0.25mg, maintenance dose 1mg

SGLT2 inhibitor

Intervention Type DRUG

dapagliflozin: oral administration from 5 to 10mg/day

Other treatments

Patients not under SGLT2i or GLP-1RA/Tirzepatide influence, but receiving other treatments that are part of CKD and diabetes standard care

No interventions assigned to this group

Dual GIP GLP-1RA

Patients receiving tirzepatide: weekly administration, subcutaneous form, starting dose 2.5mg, maintenance 5mg

Tirzepatide

Intervention Type DRUG

subcutaneous injection: starting dose 2.5 mg, maintenance 5mg (weekly administration)

Other drugs

Intervention Type DRUG

Patients not under SGLT2i or GLP-1RA influence, but receiving other treatments which are part of CKD standard care: mineralocorticoid receptor agonists, metformin, ACE inhibitors, ARBs...

Interventions

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GLP-1 receptor agonist

Semaglutide: weekly subcutaneous administration, starting dose 0.25mg, maintenance dose 1mg

Intervention Type DRUG

SGLT2 inhibitor

dapagliflozin: oral administration from 5 to 10mg/day

Intervention Type DRUG

Tirzepatide

subcutaneous injection: starting dose 2.5 mg, maintenance 5mg (weekly administration)

Intervention Type DRUG

Other drugs

Patients not under SGLT2i or GLP-1RA influence, but receiving other treatments which are part of CKD standard care: mineralocorticoid receptor agonists, metformin, ACE inhibitors, ARBs...

Intervention Type DRUG

Other Intervention Names

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semaglutide liraglutide dulaglutide exenatide dapagliflozin empagliflozin canagliflozin ARBs ACE inhibitors Metformin DPP4i non steroidal mineralocorticoid receptor agonists

Eligibility Criteria

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Inclusion Criteria

* \> or = 18 years of age
* diagnosed with CKD in stages G1, G2, G3a, G3b, and G4, not candidate for dialysis
* had uncontrolled T2DM, CVDs and/or obesity
* willing to participate in the study and sign informed consent

Exclusion Criteria

* Age \<18 years
* pregnancy
* CKD in stage G5 or G4 candidate for dialysis
* neuropsychiatric diseases preventing the patient from understanding the benefits/risks associated with the project
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cardenal Herrera University

OTHER

Sponsor Role lead

Responsible Party

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Ana Checa-Ros

Co-PI. PhD Lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Luis D'Marco, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardenal Herrera University

Ana Checa-Ros, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardenal Herrera University

Locations

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Vithas Valencia Consuelo

Valencia, Valencia, Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Ana Checa-Ros, MD, PhD

Role: CONTACT

Phone: +34 961369000

Email: [email protected]

Luis D'Marco, MD, PhD

Role: CONTACT

Phone: +34 961369000

Email: [email protected]

Facility Contacts

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Luis D'Marco, MD, PhD

Role: primary

References

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Study Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Analytic Code

View Document

Related Links

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Other Identifiers

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23/424

Identifier Type: -

Identifier Source: org_study_id