Liraglutide Treatment to Patients With Severe Renal Insufficiency

Study Overview
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Brief Summary
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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

Official Title
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Safety and Effect of Liraglutide in Patients With Type 2 Diabetes and Severe Renal Insufficiency

Conditions
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Type 2 Diabetes Mellitus, End-stage Renal Disease

Intervention / Treatment
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* Drug: Liraglutide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: T2D, Dialysis, Liraglutide<br>Daily liraglutide treatment Chronic dialysis treatment | Drug: Liraglutide<br>* Daily sc. injection, individual dosage<br>* Other names: Victoza;|
| Placebo Comparator: T2D, Dialysis, Placebo<br>Daily placebo Chronic dialysis treatment | Drug: Liraglutide<br>* Daily sc. injection, individual dosage<br>* Other names: Victoza;|
| Active Comparator: T2D, Normal kidney function, Liraglutide<br>Daily Liraglutide treatment Normal kidney function | Drug: Liraglutide<br>* Daily sc. injection, individual dosage<br>* Other names: Victoza;|
| Placebo Comparator: T2D, Normal kidney function, Placebo<br>Daily placebo treatment Normal kidney function | Drug: Liraglutide<br>* Daily sc. injection, individual dosage<br>* Other names: Victoza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma liraglutide concentration (pmol/L) | Plasma liraglutide concentration evaluated over time during continuous intervention | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycaemia; minor or major | Number of hypoglycaemic episodes during intervention. Minor (blood glucose <3.1 mmol/L, no need for assistance). Major (blood glucose <3.1 mmol/L, assistance from third person required) | 12 weeks | 
| Glycaemic control | Glycaemic control evaluated from 3 daily measurements of blood glucose, from 4 periods of 24-hour tissue glucose measurements (5 days each) and from HbA1c during the intervention period. | 12 weeka | 
| Pancreatic beta-cell function | Pancreatic beta-cell function evaluated from insulin- and C-peptide-secretion during a standard meal test 3 times during the intervention period. | 12 weeks | 
| Cardiovascular risk factors (lipids and blood pressure) | Blood pressure will be evaluated at each visit and lipid profile (HDL, LDL, total cholesterol and triglyceride) 3 times during the intervention period. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liraglutide, Uremia, Dialysis, Type 2 diabetes mellitus, Safety, Efficacy