Liraglutide Treatment to Patients With Severe Renal Insufficiency

NCT01394341 | Completed Phase 4 DMC

• 2 other identifiers: H-3-2011-0322010-021922-36
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

Incretin-based therapy for the treatment of patients with type 2 diabetes mellitus (T2D) is new and fundamentally different from the classical treatments with oral antidiabetic agents and insulin. The novel and original aspect of this investigator-initiated study is the focus on treatment with an incretin-based agent (the GLP-1 analogue liraglutide) in T2D patients with severely reduced kidney function. At present there is virtually no knowledge of the physiology and clinical implications of the role of incretin hormones and incretin-based therapy in this group of diabetic patients.The aim of the study is to establish an evidence-based rationale for introducing a GLP-1 analogue to the limited armamentarium of antidiabetic drugs for patients with type T2D and severe renal insufficiency. The overall hypothesis is that patients with T2D and severe renal insufficiency will tolerate and benefit from treatment with the GLP-1 analogue liraglutide, hereby improving glycaemic control and reducing risk factors of cardiovascular disease

Conditions

Type 2 Diabetes Mellitus; End-stage Renal Disease

Keywords

Liraglutide; Uremia; Dialysis; Type 2 diabetes mellitus; Safety; Efficacy

Outcome Measures

Primary Outcomes (1)

• Plasma liraglutide concentration (pmol/L)

  Plasma liraglutide concentration evaluated over time during continuous intervention

  12 weeks

Secondary Outcomes (4)

• Hypoglycaemia; minor or major

  12 weeks

• Glycaemic control

  12 weeka

• Pancreatic beta-cell function

  12 weeks

• Cardiovascular risk factors (lipids and blood pressure)

  12 weeks

Study Arms (4)

T2D, Dialysis, Liraglutide

ACTIVE COMPARATOR

Daily liraglutide treatment Chronic dialysis treatment

Drug: Liraglutide

T2D, Dialysis, Placebo

PLACEBO COMPARATOR

Daily placebo Chronic dialysis treatment

Drug: Liraglutide

T2D, Normal kidney function, Liraglutide

ACTIVE COMPARATOR

Daily Liraglutide treatment Normal kidney function

Drug: Liraglutide

T2D, Normal kidney function, Placebo

PLACEBO COMPARATOR

Daily placebo treatment Normal kidney function

Drug: Liraglutide

Interventions

Liraglutide DRUG

Daily sc. injection, individual dosage

Also known as: Victoza

T2D, Dialysis, Liraglutide; T2D, Dialysis, Placebo; T2D, Normal kidney function, Liraglutide; T2D, Normal kidney function, Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; aged 18-85 years
• End-stage renal disease
• Chronic dialysis treatment (minimum 3 months)
• T2D (diagnosed according to WHO criteria)
• Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones) and/or insulin
• Documented beta cell function (evaluated by a glucagon test)
• Male or female; aged 18-85 years
• Normal kidney function: Plasma creatinine \<0.105 mmol/L for men and \<0.090 mmol/L for women
• T2D (diagnosed according to WHO criteria)
• Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones) and/or insulin
• Documented beta cell function (evaluated by a glucagon test)
• Hemoglobin A1c ≥6.5%

You may not qualify if:

• Type 1 diabetes mellitus
• Chronic pancreatitis / previous acute pancreatitis
• Known or suspected hypersensitivity to trial product(s) or related products
• Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors or other drugs, which in the Investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening
• Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder which in the investigators' opinion could interfere with the results of the trial
• Inflammatory bowel disease
• Cardiac disease defined as: decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months
• Body mass index ≤ 18.5 kg/m2 or ≥ 50.0 kg/m2
• Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
• Clinical signs of diabetic gastroparesis
• Impaired liver function (transaminases \>two times upper reference levels)
• Receipt of any investigational product 90 days prior to this trial
• Known or suspected abuse of alcohol or narcotics
• Screening calcitonin ≥50 ng/l
• Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

Sponsors & Collaborators

• Bo Feldt-Rasmussen: lead
• Novo Nordisk A/S: collaborator
• The GCP unit at Copenhagen University Hospital: collaborator

Study Sites (3)

Department of Endocrinology PE, Copenhagen University Hospital, Rigshospitalet

Copenhagen Ø, Copenhagen, 2100, Denmark

Location

Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet

Copenhagen Ø, Copenhagen, 2100, Denmark

Location

Department of Internal Medicine H, Hillerød Hospital

Hillerød, 3400, Denmark

Location

Related Publications (3)

• 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

• Idorn T, Knop FK, Jorgensen MB, Jensen T, Resuli M, Hansen PM, Christensen KB, Holst JJ, Hornum M, Feldt-Rasmussen B. Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease: An Investigator-Initiated, Placebo-Controlled, Double-Blind, Parallel-Group, Randomized Trial. Diabetes Care. 2016 Feb;39(2):206-13. doi: 10.2337/dc15-1025. Epub 2015 Aug 17.

  PMID: 26283739 DERIVED

• Idorn T, Knop FK, Jorgensen M, Jensen T, Resuli M, Hansen PM, Christensen KB, Holst JJ, Hornum M, Feldt-Rasmussen B. Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease: protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded, parallel intervention study. BMJ Open. 2013 Apr 26;3(4):e002764. doi: 10.1136/bmjopen-2013-002764. Print 2013.

  PMID: 23624993 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Kidney Failure, Chronic; Uremia

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency, Chronic; 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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Bo Feldt-Rasmussen, Prof, DMSc

  Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet

  STUDY DIRECTOR

• Thomas Idorn, MD

  Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSc, Head of Department

Study Record Dates

• First Submitted: July 11, 2011
• First Posted: July 14, 2011
• Study Start: September 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 9, 2013

Record last verified: 2013-10

Locations

DK (3)