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

NCT07309094 | Recruiting FDA Drug

• 1 other identifier: 23/424
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Ultrasonography change in perirenal adipose tissue thickness

  Change in perirenal adipose tissue thickness as measured with ultrasonography

  16 months

• Change in estimated glomerular filtration rate

  Change in eGFR as per the CKD-EPI formula

  16 months

Secondary Outcomes (10)

• Ultrasonographic Change in epicardial adipose tissue thickness

  16 months

• Change in serum leptin levels

  16 months

• Change in visceral fat area

  16 months

• Ultrasonographic Change in subcutaneous adipose tissue

  16 months

• Ultrasonographic Change in preperitoneal adipose tissue thickness

  16 months

Other Outcomes (3)

• Change in systemic inflammation markers

  16 months

• Change in systemic inflammation markers

  16 months

• Change in systemic inflammation markers

  16 months

Study Arms (4)

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)

Drug: GLP-1 receptor agonist; Drug: SGLT2 inhibitor

SGLT2i Cohort

There will also be another comparative group of patients under SGLT2i

Drug: GLP-1 receptor agonist; Drug: SGLT2 inhibitor

Other treatments

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

Dual GIP GLP-1RA

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

Drug: Tirzepatide; Drug: Other drugs

Interventions

GLP-1 receptor agonist DRUG

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

Also known as: semaglutide, liraglutide, dulaglutide, exenatide

GLP-1RA Cohort; SGLT2i Cohort

SGLT2 inhibitor DRUG

dapagliflozin: oral administration from 5 to 10mg/day

Also known as: dapagliflozin, empagliflozin, canagliflozin

GLP-1RA Cohort; SGLT2i Cohort

Tirzepatide DRUG

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

Dual GIP GLP-1RA

Other drugs 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...

Also known as: ARBs, ACE inhibitors, Metformin, DPP4i, non steroidal mineralocorticoid receptor agonists

Dual GIP GLP-1RA

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be assigned to the different groups according to current treatment criteria: SGLT2i: patients with CKD and T2DM with an eGFR ≥20ml/min/1.73m2; patients with CKD and eGFR ≥20ml/min/1.73m2, accompanied by an urinary albumin-to-creatinine ratio (ACR) ≥200mg/g; patients with CKD and heart failure, irrespective of level of albuminuria; or subjects with CKD and eGFR 20-45ml/min/1.73m2, with ACR \<200mg/g. GLP-1RA/tirzepatide: In patients with T2D and CKD who have not achieved individualized glycemic targets despite use of metformin and SGLT2i treatment, or who are unable to use those medications. Other treatments: patients not meeting the criteria to be treated with SGLT2i or GLP-1RA/tirzepatide

You may qualify if:

• \> 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cardenal Herrera University: lead

Study Sites (1)

Vithas Valencia Consuelo

Valencia, Valencia, 46007, Spain

RECRUITING

Related Publications (15)

• Zhao L, Li W, Zhang P, Wang D, Yang L, Yuan G. Liraglutide induced browning of visceral white adipose through regulation of miRNAs in high-fat-diet-induced obese mice. Endocrine. 2024 Jul;85(1):222-232. doi: 10.1007/s12020-024-03734-2. Epub 2024 Feb 20.

  PMID: 38378894 BACKGROUND

• Ying Y, Zhu H, Liang Z, Ma X, Li S. GLP1 protects cardiomyocytes from palmitate-induced apoptosis via Akt/GSK3b/b-catenin pathway. J Mol Endocrinol. 2015 Dec;55(3):245-62. doi: 10.1530/JME-15-0155. Epub 2015 Sep 18.

  PMID: 26386043 BACKGROUND

• Carraro-Lacroix LR, Malnic G, Girardi AC. Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Renal Physiol. 2009 Dec;297(6):F1647-55. doi: 10.1152/ajprenal.00082.2009. Epub 2009 Sep 23.

  PMID: 19776173 BACKGROUND

• Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, Baeres FMM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R; FLOW Trial Committees and Investigators. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024 Jul 11;391(2):109-121. doi: 10.1056/NEJMoa2403347. Epub 2024 May 24.

  PMID: 38785209 BACKGROUND

• Giugliano D, Maiorino MI, Bellastella G, Longo M, Chiodini P, Esposito K. GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials. Diabetes Obes Metab. 2019 Nov;21(11):2576-2580. doi: 10.1111/dom.13847. Epub 2019 Aug 28.

  PMID: 31373167 BACKGROUND

• D'Marco L, Puchades MJ, Panizo N, Romero-Parra M, Gandia L, Gimenez-Civera E, Perez-Bernat E, Gonzalez-Rico M, Gorriz JL. Cardiorenal Fat: A Cardiovascular Risk Factor With Implications in Chronic Kidney Disease. Front Med (Lausanne). 2021 May 25;8:640814. doi: 10.3389/fmed.2021.640814. eCollection 2021.

  PMID: 34113631 BACKGROUND

• Ku E, Lee BJ, Wei J, Weir MR. Hypertension in CKD: Core Curriculum 2019. Am J Kidney Dis. 2019 Jul;74(1):120-131. doi: 10.1053/j.ajkd.2018.12.044. Epub 2019 Mar 19.

  PMID: 30898362 BACKGROUND

• Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6.

  PMID: 19896746 BACKGROUND

• Khan MZ, Syed M, Osman M, Faisaluddin M, Sulaiman S, Farjo PD, Khan MU, Agrawal P, Alharbi A, Khan SU, Munir MB, Balla S. Contemporary Trends and Outcomes in Patients With ST-Segment Elevation Myocardial Infarction and End-Stage Renal Disease on Dialysis: Insight from the National Inpatient Sample. Cardiovasc Revasc Med. 2020 Dec;21(12):1474-1481. doi: 10.1016/j.carrev.2020.05.004. Epub 2020 May 11.

  PMID: 32444271 BACKGROUND

• Moisi MI, Bungau SG, Vesa CM, Diaconu CC, Behl T, Stoicescu M, Toma MM, Bustea C, Sava C, Popescu MI. Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease. Diagnostics (Basel). 2021 Aug 23;11(8):1518. doi: 10.3390/diagnostics11081518.

  PMID: 34441451 BACKGROUND

• Artzi-Medvedik R, Kob R, Fabbietti P, Lattanzio F, Corsonello A, Melzer Y, Roller-Wirnsberger R, Wirnsberger G, Mattace-Raso F, Tap L, Gil P, Martinez SL, Formiga F, Moreno-Gonzalez R, Kostka T, Guligowska A, Arnlov J, Carlsson AC, Freiberger E, Melzer I; SCOPE investigators. Impaired kidney function is associated with lower quality of life among community-dwelling older adults : The screening for CKD among older people across Europe (SCOPE) study. BMC Geriatr. 2020 Oct 2;20(Suppl 1):340. doi: 10.1186/s12877-020-01697-3.

  PMID: 33008306 BACKGROUND

• George LK, Koshy SKG, Molnar MZ, Thomas F, Lu JL, Kalantar-Zadeh K, Kovesdy CP. Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function. Circ Heart Fail. 2017 Aug;10(8):e003825. doi: 10.1161/CIRCHEARTFAILURE.116.003825.

  PMID: 28765150 BACKGROUND

• GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020 Feb 29;395(10225):709-733. doi: 10.1016/S0140-6736(20)30045-3. Epub 2020 Feb 13.

  PMID: 32061315 BACKGROUND

• Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M, Pletcher MA, Smith AE, Tang K, Yuan CW, Brown JC, Friedman J, He J, Heuton KR, Holmberg M, Patel DJ, Reidy P, Carter A, Cercy K, Chapin A, Douwes-Schultz D, Frank T, Goettsch F, Liu PY, Nandakumar V, Reitsma MB, Reuter V, Sadat N, Sorensen RJD, Srinivasan V, Updike RL, York H, Lopez AD, Lozano R, Lim SS, Mokdad AH, Vollset SE, Murray CJL. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018 Nov 10;392(10159):2052-2090. doi: 10.1016/S0140-6736(18)31694-5. Epub 2018 Oct 16.

  PMID: 30340847 BACKGROUND

• Borg R, Carlson N, Sondergaard J, Persson F. The Growing Challenge of Chronic Kidney Disease: An Overview of Current Knowledge. Int J Nephrol. 2023 Mar 1;2023:9609266. doi: 10.1155/2023/9609266. eCollection 2023.

  PMID: 36908289 BACKGROUND

Related Links

• Research group website

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples Serum samples Urine samples

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Obesity; Diabetes Mellitus, Type 2; Inflammation

Interventions

semaglutide; Liraglutide; dulaglutide; Exenatide; Sodium-Glucose Transporter 2 Inhibitors; dapagliflozin; empagliflozin; Canagliflozin; Tirzepatide; Angiotensin-Converting Enzyme Inhibitors; Metformin

Condition Hierarchy (Ancestors)

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; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Protease Inhibitors; Enzyme Inhibitors; Biguanides; Guanidines; Amidines

Study Officials

• Luis D'Marco, MD, PhD

  Cardenal Herrera University

  PRINCIPAL INVESTIGATOR

• Ana Checa-Ros, MD, PhD

  Cardenal Herrera University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana Checa-Ros, MD, PhD

CONTACT

+34 961369000; ana.checaros@uchceu.es

Luis D'Marco, MD, PhD

CONTACT

+34 961369000; luis.dmarcogascon@uchceu.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-PI. PhD Lecturer

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: December 30, 2025
• Study Start: September 15, 2023
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)