Liraglutide Treatment to Patients With Severe Renal Insufficiency

Bo Feldt-Rasmussen

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes Mellitus; End-stage Renal Disease

Treatments: Drug: Liraglutide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01394341

H-3-2011-032

2010-021922-36 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 40 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria - patients with T2D in dialysis

• 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)

Inclusion criteria - patients with T2D and normal kidney function

• 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%

Exclusion Criteria - both groups

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 4 patient groups, including a placebo group

T2D, Dialysis, Liraglutide

Active Comparator group

Description:

Daily liraglutide treatment Chronic dialysis treatment

Treatment:

Drug: Liraglutide

T2D, Dialysis, Placebo

Placebo Comparator group

Description:

Daily placebo Chronic dialysis treatment

Treatment:

Drug: Liraglutide

T2D, Normal kidney function, Liraglutide

Active Comparator group

Description:

Daily Liraglutide treatment Normal kidney function

Treatment:

Drug: Liraglutide

T2D, Normal kidney function, Placebo

Placebo Comparator group

Description:

Daily placebo treatment Normal kidney function

Treatment:

Drug: Liraglutide