Effects of Liraglutide on Kidney Function in Type 2 Diabetic Patients

Study Overview
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Brief Summary
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Recent studies in rodents show that glucagon-like peptide-1 (GLP-1) analogues protect against diabetic nephropathy. We hypothesise that this is also the case in humans. This study will investigate the short-term effect of liraglutide (GLP-1 analogue) on the kidneys in type 2 diabetic patients. Impact on basic kidney physiological will be determined and kidney injury markers will be measured as surrogate parameters of kidney protection.

Official Title
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A Randomised, Double-blinded, Cross-over Study Investigating the Short-term Impact of Liraglutide on Kidney Function in Diabetic Patients

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Placebo-liraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Male gender T2DM, diagnosed according to international guidelines Age 20-60 years, both included Body Mass Index (BMI): 20-32 kg/m2, both included Metformin treatment Albumin/creatinine ratio <25 mg/mmol Exclusion Criteria: Known or suspected allergy to trial product or related products Previous participation in this trial Previous treatment with GLP-1 analogues or DPP-4 inhibitors Current treatment with any antidiabetic drug other than metformin Poorly regulated glycemic control (HbA1c > 8%) Impaired kidney function: estimated GFR < 70ml/min Impaired liver function: liver parameters exceed 2 times upper normal limit Subjects with active malignancy Severe cardiac insufficiency classified according to NYHA III-IV Unstable angina pectoris, acute myocardial infarction (AMI) within the last 12 months Severe, uncontrolled hypertension: sitting blood pressure (BP) > 180/110 mmHg Antihypertensive treatment consisting of more than two different pharmaceutical products Symptoms related to benign prostate hyperplasia Claustrophobia Any metal body implants History of pancreatitis, type 1 diabetes, gastroparesis or multiple endocrine neoplasia syndrome type 2 Personal or family history of medullary thyroid carcinoma Any diseases judged by the investigator that could affect the trial Any medication judged by the investigator that could affect the trial

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br>1.2 mg liraglutide sc. (single-dose) | Drug: Liraglutide<br> <br> * Other names: Victoza;|
| Placebo Comparator: Placebo-liraglutide<br>Placebo liraglutide sc. (single-dose) | Drug: Placebo-liraglutide<br> <br> * Other names: Isotonic saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular Filtration Rate (51Cr-EDTA plasma clearance) |  | 10-15 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Blood Flow (functional magnetic resonance imaging) |  | 15 hours post-dose | 
| Renal electrolyte clearance | Sodium, potassium, calcium, lithium and osmotically active substances. | 10-15 hours post-dose | 
| Excretion of kidney injury markers | Albumin, NGAL, KIM-1, angiotensinogen and 8-OHdG. | 0-10 hours and 10-15 hours post-dose | 
| Plasma concentrations of various hormones | Angiotensin II, renin, aldosterone, atrial natriuretic peptide, catecholamines. | 10-15 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liraglutide, victoza, GLP-1, kidney, diabetes, renal, diabetic nephropathy