Diabetic Kidney Disease
Conditions
Keywords
kidney, diabetes, glp-1
Brief summary
Diabetic kidney disease (DKD) is a devastating complication of diabetes, that in it's worst form, can lead to early cardiovascular death or kidney failure. A group of medicines used to treat diabetes, glucagon-like-peptide-1 analogues (GLP-1), may be able to protect people with diabetes from DKD by reducing inflammation in the kidney. This study aims to test this theory by studying the effect of GLP-1 on kidney function in people with diabetes. To understand how GLP-1 can affect inflammation, the investigators will give a GLP-1 treatment (Liraglutide) to people with DKD and monitor the effect on inflammation and kidney function using blood and urine tests. The investigators will compare these results to patients with DKD who do not receive GLP-1 treatment. If GLP-1 proves to be effective in reducing inflammation and improving kidney function, then it could be developed as a viable new treatment for people with DKD, and may significantly reduce the disease burden, or the risk of DKD, in people with diabetes. This would be a major advance in the treatment of DKD.
Detailed description
A randomised controlled trial for patients with microalbuminuria and type 2 diabetes. Treatment is 0.6mg of liraglutide and is compared to standard care. Treatment duration is 6 months.
Interventions
DRUGLiraglutide
Daily administration of liraglutide for 6 months
Sponsors
University College Dublin
Karl Neff
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes with a HbA1c of 42-75mmol/mol (6-9%DCCT) * Male or female aged above 30 years * Have a negative pregnancy test at screening (women of child bearing potential only) * Body mass index (BMI) of 25kg/m2 or greater * On a renin-angiotensin system antagonist, at a stable dose, for at least 8 weeks before inclusion into the study * Established microalbuminuria * Estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 or above by Modification of Diet in Renal Disease (MDRD) formula
Exclusion criteria
* Patients with any cognitive impediment that preclude the patient from giving free and informed consent * Patients on dipeptidyl peptidase 4 inhibitors or thiazolidinedione treatment * Patients with stage 4-5 renal disease, defined as an eGFR of 30ml/min/1.73m2 or less * Patients who have used a GLP-1 agent in the last 6 months * Female patients of child bearing potential who are pregnant, breastfeeding, or unwilling to practice an acceptable barrier and/or hormonal method of contraception or abstinence during participation in the study * Previous pancreatitis * Hypersensitivity to GLP-1 analogues * Proliferative diabetic retinopathy * Any other contraindications, as per the SmPC for liraglutide * Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the dosing requirements * Concurrent treatment with an investigational drug or participation in another clinical trial * Use of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational medicinal product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MCP-1:Creatinine Ratio in Urine | Up to 26 weeks | Spot urine sample for MCP-1 and creatinine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine Albumin:Creatinine Ratio | Up to 26 weeks | Spot urine sample for albumin and creatinine |
| Urinary Albumin Excretion Rate | Up to 26 weeks | Albuminuria as Measured by 24 Hour Albumin Excretion Rate |
| sCD163 in Serum | Up to 26 weeks | Serum sample for sCD163 |
| sCD163:Creatinine Ratio in Urine | Up to 26 weeks | Spot urine sample for MCP-1 and creatinine |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety in All Participants as Measured by Adverse Event Rate | Up to 34 weeks | Adverse event data collection |
Countries
Ireland
Participant flow
Recruitment details
All subjects were recruited from St Vincent's University Hospital, Dublin, Ireland
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide Liraglutide 0.6 mg daily administration for 6 months | 10 |
| Control Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Control | Liraglutide | Total |
|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 10 | 65 years STANDARD_DEVIATION 7 | 65 years STANDARD_DEVIATION 9 |
| BMI | 34 kg/m2 STANDARD_DEVIATION 4 | 30 kg/m2 STANDARD_DEVIATION 5 | 32 kg/m2 STANDARD_DEVIATION 5 |
| Diastolic Blood Pressure | 81 mmHg STANDARD_DEVIATION 12 | 82 mmHg STANDARD_DEVIATION 8 | 81 mmHg STANDARD_DEVIATION 10 |
| Duration of diabetes | 9 years STANDARD_DEVIATION 2 | 8 years STANDARD_DEVIATION 1 | 9 years STANDARD_DEVIATION 2 |
| Estimated glomerular filtration rate | 79 ml/min/1.73m2 STANDARD_DEVIATION 11 | 69 ml/min/1.73m2 STANDARD_DEVIATION 7 | 74 ml/min/1.73m2 STANDARD_DEVIATION 10 |
| HbA1c | 52 mmol/mol STANDARD_DEVIATION 7 | 53 mmol/mol STANDARD_DEVIATION 7 | 53 mmol/mol STANDARD_DEVIATION 7 |
| MCP-1:Creatinine Ratio in Urine | 20.8 ng/mmol STANDARD_DEVIATION 6 | 32.8 ng/mmol STANDARD_DEVIATION 25.7 | 27.2 ng/mmol STANDARD_DEVIATION 19.6 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Ireland | 10 Participants | 10 Participants | 20 Participants |
| sCD163:creatinine ratio in urine | 37 pg/mmol STANDARD_DEVIATION 38 | 51 pg/mmol STANDARD_DEVIATION 60 | 44 pg/mmol STANDARD_DEVIATION 51 |
| sCD163 in serum | 106 ng/ml STANDARD_DEVIATION 47 | 96 ng/ml STANDARD_DEVIATION 45 | 100 ng/ml STANDARD_DEVIATION 45 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
| Systolic blood pressure | 140 mmHg STANDARD_DEVIATION 20 | 136 mmHg STANDARD_DEVIATION 14 | 138 mmHg STANDARD_DEVIATION 17 |
| Urinary albumin excretion rate | 122.8 µg/min STANDARD_DEVIATION 142.1 | 106.9 µg/min STANDARD_DEVIATION 109.5 | 114.9 µg/min STANDARD_DEVIATION 123.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 1 / 10 |
| other Total, other adverse events | 8 / 10 | 7 / 10 |
| serious Total, serious adverse events | 1 / 10 | 1 / 10 |
Outcome results
Primary
MCP-1:Creatinine Ratio in Urine
Spot urine sample for MCP-1 and creatinine
Time frame: Up to 26 weeks
Population: Liraglutide group contained an analytical outlier which was excluded from further analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | MCP-1:Creatinine Ratio in Urine | 27.9 ng/mmol | Standard Deviation 14.3 |
| Control | MCP-1:Creatinine Ratio in Urine | 24.3 ng/mmol | Standard Deviation 15.4 |
Secondary
sCD163:Creatinine Ratio in Urine
Spot urine sample for MCP-1 and creatinine
Time frame: Up to 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | sCD163:Creatinine Ratio in Urine | 27.9 pg/mmol | Standard Deviation 14 |
| Control | sCD163:Creatinine Ratio in Urine | 24.3 pg/mmol | Standard Deviation 15.4 |
Secondary
sCD163 in Serum
Serum sample for sCD163
Time frame: Up to 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | sCD163 in Serum | 82 ng/ml | Standard Deviation 34 |
| Control | sCD163 in Serum | 84 ng/ml | Standard Deviation 23 |
Secondary
Urinary Albumin Excretion Rate
Albuminuria as Measured by 24 Hour Albumin Excretion Rate
Time frame: Up to 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Urinary Albumin Excretion Rate | 144.1 µg/min | Standard Deviation 232.6 |
| Control | Urinary Albumin Excretion Rate | 132.4 µg/min | Standard Deviation 101.3 |
Secondary
Urine Albumin:Creatinine Ratio
Spot urine sample for albumin and creatinine
Time frame: Up to 26 weeks
Other Pre-specified
Safety in All Participants as Measured by Adverse Event Rate
Adverse event data collection
Time frame: Up to 34 weeks