The Effect of Glucagon-like-peptide 1 (GLP-1) Receptor Agonism on Diabetic Kidney Disease

NCT01847313 | Completed Phase 3 Results DMC

• 1 other identifier: GLP-1-2012-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic kidney disease (DKD) is a devastating complication of diabetes, that in it's worst form, can lead to early cardiovascular death or kidney failure. A group of medicines used to treat diabetes, glucagon-like-peptide-1 analogues (GLP-1), may be able to protect people with diabetes from DKD by reducing inflammation in the kidney. This study aims to test this theory by studying the effect of GLP-1 on kidney function in people with diabetes. To understand how GLP-1 can affect inflammation, the investigators will give a GLP-1 treatment (Liraglutide) to people with DKD and monitor the effect on inflammation and kidney function using blood and urine tests. The investigators will compare these results to patients with DKD who do not receive GLP-1 treatment. If GLP-1 proves to be effective in reducing inflammation and improving kidney function, then it could be developed as a viable new treatment for people with DKD, and may significantly reduce the disease burden, or the risk of DKD, in people with diabetes. This would be a major advance in the treatment of DKD.

Conditions

Diabetic Kidney Disease

Keywords

kidney; diabetes; glp-1

Outcome Measures

Primary Outcomes (1)

• MCP-1:Creatinine Ratio in Urine

  Spot urine sample for MCP-1 and creatinine

  Up to 26 weeks

Secondary Outcomes (4)

• Urine Albumin:Creatinine Ratio

  Up to 26 weeks

• Urinary Albumin Excretion Rate

  Up to 26 weeks

• sCD163 in Serum

  Up to 26 weeks

• sCD163:Creatinine Ratio in Urine

  Up to 26 weeks

Other Outcomes (1)

• Safety in All Participants as Measured by Adverse Event Rate

  Up to 34 weeks

Study Arms (2)

Liraglutide

ACTIVE COMPARATOR

Liraglutide 0.6 mg daily

Drug: Liraglutide

Control

NO INTERVENTION

Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist

Interventions

Liraglutide DRUG

Daily administration of liraglutide for 6 months

Also known as: Glucagon like peptide 1 receptor agonist, NN2211

Liraglutide

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes with a HbA1c of 42-75mmol/mol (6-9%DCCT)
• Male or female aged above 30 years
• Have a negative pregnancy test at screening (women of child bearing potential only)
• Body mass index (BMI) of 25kg/m2 or greater
• Established microalbuminuria
• Estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 or above by Modification of Diet in Renal Disease (MDRD) formula

You may not qualify if:

• Patients with any cognitive impediment that preclude the patient from giving free and informed consent
• Patients on dipeptidyl peptidase 4 inhibitors or thiazolidinedione treatment
• Patients with stage 4-5 renal disease, defined as an eGFR of 30ml/min/1.73m2 or less
• Patients who have used a GLP-1 agent in the last 6 months
• Female patients of child bearing potential who are pregnant, breastfeeding, or unwilling to practice an acceptable barrier and/or hormonal method of contraception or abstinence during participation in the study
• Previous pancreatitis
• Hypersensitivity to GLP-1 analogues
• Proliferative diabetic retinopathy
• Any other contraindications, as per the SmPC for liraglutide
• Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the dosing requirements
• Concurrent treatment with an investigational drug or participation in another clinical trial
• Use of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational medicinal product

Sponsors & Collaborators

• Karl Neff: lead
• University College Dublin: collaborator

Study Sites (1)

St Vincent's Healthcare Group

Dublin, Dublin 4, Ireland

Location

Related Publications (25)

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  PMID: 22608055 BACKGROUND

• Miras AD, Chuah LL, Lascaratos G, Faruq S, Mohite AA, Shah PR, Gill M, Jackson SN, Johnston DG, Olbers T, le Roux CW. Bariatric surgery does not exacerbate and may be beneficial for the microvascular complications of type 2 diabetes. Diabetes Care. 2012 Dec;35(12):e81. doi: 10.2337/dc11-2353. No abstract available.

  PMID: 23173142 BACKGROUND

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  PMID: 22517736 BACKGROUND

• Pinkney J, Fox T, Ranganath L. Selecting GLP-1 agonists in the management of type 2 diabetes: differential pharmacology and therapeutic benefits of liraglutide and exenatide. Ther Clin Risk Manag. 2010 Sep 7;6:401-11. doi: 10.2147/tcrm.s7313.

  PMID: 20856686 BACKGROUND

• Jacobsen LV, Hindsberger C, Robson R, Zdravkovic M. Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br J Clin Pharmacol. 2009 Dec;68(6):898-905. doi: 10.1111/j.1365-2125.2009.03536.x.

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• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

  PMID: 39963952 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Prof Carel le Roux
• Organization: University College Dublin

carel.leroux@ucd.ie

+353 1 716 6831

Study Officials

• Carel le Roux, MBBS PhD

  University College Dublin

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Research Fellow

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 6, 2013
• Study Start: April 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 8, 2019
• Results First Posted: February 8, 2019

Record last verified: 2018-09

Locations

IE (1)