Clinical trial NCT02545738: Antiproteinuric Effects of Liraglutide Treatment
Official title: Antiproteinuric Effects of Liraglutide Treatment in Patients With Type 2 Diabetes and Albuminuria: A Randomised, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Kidney Disease
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2015-09-10
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine the effect of Liraglutide on albuminuria in type 2 diabetes.

Detailed description: Initial findings point to a clinically significant antiproteinuric effect of liraglutide treatment, possibly independent from blood pressure reduction. The mechanism behind is unclear and the magnitude of albuminuria reduction needs to be verified. Antiproteinuric effects are usually renoprotective and potentially also cardioprotective and may suggest an additional benefit from liraglutide treatment.

The aim of this study is to evaluate the magnitude of the antiproteinuric effect of short-term liraglutide treatment (12 weeks) in patients with type 2 diabetes and albuminuria. In addition, possible mechanisms causing the antiproteinuric effect will be explored.

Eligibility criteria: Inclusion Criteria:

1. Must give written informed consent before participation. Patient information and consent form must be approved by the Danish Medicines Agency and the Regional Scientific Ethical Committee
2. Male or female patients \>18 years with type 2 diabetes (WHO criteria).
3. HbA1c ≥ 48 mmol/mol (6.5 %)
4. eGFR ≥ 30 ml/min/1.73 m2 (estimated by MDRD formula)
5. Fertile female patients must use chemical, hormonal or mechanical contraceptives or be in menopause (i.e. must not have had regular menstrual bleeding for at least one year) or have undergone bilateral oophorectomi or have been surgically sterilized or hysterectomised at least six months prior to screening
6. Patients must be on stable RAAS-blocking treatment (unchanged dose 4 weeks before inclusion)
7. Geometic mean urine albumin-to-creatinine ratio (UACR) above 30 mg/g at screening (measured in at least two of three consecutive morning spot urine samples)
8. Systolic blood pressure (SBP) must be lower than 180 mm Hg at screening.
9. Patients must be on stable glucose lowering medication for at least two weeks before the first visit.
10. Must be able to communicate with the investigator.

Exclusion Criteria:

1. SBP \> 180 mm Hg at screening
2. Type 1 diabetes mellitus
3. Chronic pancreatitis / previous acute pancreatitis
4. Known or suspected hypersensitivity to trial product(s) or related products.
5. Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon like peptide-1 agonists and sodium-glucose co-transporter 2 (SGLT-2) inhibitors, which in the investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening
6. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial
7. Inflammatory bowel disease
8. 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
9. Previous bowel resection
10. Body mass index \<18.5 kg/m2
11. Females of childbearing potential who are pregnant, breast-feeding, intending to become pregnant or not using adequate contraceptive methods
12. Clinical signs of diabetic gastroparesis
13. Impaired liver function (transaminases \> two times upper reference levels)
14. The receipt of any investigational product 90 days prior to this trial
15. Known or suspected abuse of alcohol or narcotics
16. Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

Primary outcomes:
measure: Change in albuminuria
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in renin-angiotensin system hormones
timeFrame: 24 weeks
measure: Change in kidney function
timeFrame: 24 weeks
measure: Change in 24h blood pressure
timeFrame: 24 weeks
measure: Change in markers of inflammation
timeFrame: 24 weeks
measure: 24h heart rate
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Peter Rossing
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Peter Rossing, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: von Scholten BJ, Persson F, Rosenlund S, Hovind P, Faber J, Hansen TW, Rossing P. The effect of liraglutide on renal function: A randomized clinical trial. Diabetes Obes Metab. 2017 Feb;19(2):239-247. doi: 10.1111/dom.12808. Epub 2016 Nov 21.