The Effect of Liraglutide in Patients With Prediabetes and Kidney Failure

Study Overview
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Brief Summary
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The present study will examine the effects of liraglutide treatment during 26 weeks on several cardiovascular risk factors in patients with prediabetes and end-stage renal disease (ESRD). The primary objective is to determine the efficacy of the treatment on glucose tolerance evaluated during a 3h 75g-oral glucose tolerance test (OGTT). Secondary objectives include various clinical and biochemical cardiovascular and safety parameters. We hypothesise that treatment with liraglutide can improve glucose tolerance in prediabetic patients with ESRD by normalizing plasma glucose excursions during an OGTT and ameliorate other cardiovascular risk factors.

Official Title
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Glycaemic and Cardiovascular Efficacy of Liraglutide in Prediabetic Patients With End-stage Renal Disease

Conditions
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Kidney Failure, Chronic, Prediabetic State

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: End-stage renal disease treated with chronic maintenance dialysis (haemodialysis or peritoneal dialysis) Impaired glucose tolerance (2h plasma glucose ≥ 7,8 and < 11.1 mmol/l following a 75g-OGTT) and/or impaired fasting glucose (fasting plasma glucose ≥ 6.1 and < 7.0 mmol/l) evaluated at the screening visit Exclusion Criteria: Diabetes mellitus type 1 or type 2 (diagnose according to WHO criteria) Chronic pancreatitis / previous acute pancreatitis Known or suspected hypersensitivity to trial product(s) or related products Treatment with oral glucocorticoids, calcineurin inhibitors or incretin-based therapy 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 investigator's opinion could interfere with the results of the trial Clinical suspicion of cardiac disease currently investigated 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 (BMI) <20 kg/m2 and/or >50 kg/m2 Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods* Impaired liver function (transaminases > two times upper reference levels) The 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 Lawfully detained, institutionalised and patients who are unable to give informed consent due to physical or mental conditions will not be included. * Intrauterine devices and hormonal contraceptives (oral pills, patches, implants, vaginal rings, and injections) are considered as adequate contraceptives. Females of childbearing potential must use one of these contraceptives throughout the entire study plus 1 week after last injection with study medication. Surgical sterile (by bilateral vasectomy, tubectomy, hysterectomy or oophorectomy) or postmenopausal (defined as amenorrheic for at least one year) female participants are not considered as having a childbearing potential and are not required to use contraception.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liraglutide treatment<br>Subcutaneous, once daily injection of liraglutide, individually dosed up to 1.8 mg/day. | Drug: Liraglutide<br> <br> * Other names: Victoza;|
| Placebo Comparator: Placebo treatment<br>Subcutaneous, once daily injection of placebo, individually dosed up to 1.8 mg/day. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose during oral glucose tolerance test at week 26 | Difference between the two treatment arms in plasma glucose concentrations during a 3h 75g-OGTT on the trial visit of week 26 | The trial visit of week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemic incidents | Total hypoglycemic episodes during intervention | From the randomisation to trial visit of week 26 | 
| Fasting values of glucometabolic hormones | Fasting plasma glucose, proinsulin, insulin and glucagon | The trial visit of week 26 | 
| Insulin resistance | Insulin resistance evaluated by homeostasis model assessment (HOMA) | The trial visit of week 26 | 
| Beta cell function | Beta-cell function evaluated by HOMA | The trial visit of week 26 | 
| Change in glycemic state | Change in glycemic state following oral glucose tolerance test (normal glucose tolerance (NGT, fasting plasma glucose < 6.1 mmol/l and 2h plasma glucose < 7.8 mmol/l), impaired fasting glucose (IFG, fasting plasma glucose ≥ 6.1 and < 7.0 mmol/l), impaired glucose tolerance (IGT, 2h plasma glucose ≥ 7,8 and < 11.1 mmol/l) and diabetes mellitus (DM, fasting plasma glucose ≥ 7 mmol/l or 2h plasma glucose ≥ 11.1 mmol/l)) | The trial visit of week 26 | 
| Blood pressure | Blood Pressure | The trial visit of week 26 | 
| Pulse | Resting pulse | The trial visit of week 26 | 
| Weight | Weight | The trial visit of week 26 | 
| Body composition | Body composition by dual energy x-ray absorptiometry (DXA) scan | The trial visit of week 26 | 
| Cardiac function and perfusion | Cardiac function and perfusion evaluated by Rb-PET/CT scan | The trial visit of week 26 | 
| Cardiac autonomic function | Cardiac autonomic function evaluated by heart rate variability | The trial visit of week 26 | 
| Arterial stiffness | Arterial stiffness evaluated by Augmentation index from Pulse wave analysis | The trial visit of week 26 | 
| Cardiovascular and endothelial risk markers | Cardiovascular and endothelial risk markers (troponin T, troponin I, creatine kinase-MB, high-sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), Tissue plasminogen activator (tPA), urat, von Willebrand factor (vWF), vascular endothelial cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), TNFalpha, proBNP, E-selectin and asymmetric dimethylarginine) | The trial visit of week 26 | 
| Prothrombotic state | Prothrombotic state (fibrinogen, activated partial thromboplastin time (APTT) and thromboelastography (TEG)) | The trial visit of week 26 | 
| Lipid profile | Lipid profile | The trial visit of week 26 | 
| Plasma liraglutide | Plasma liraglutide | The trial visit of week 26 |