Clinical trial NCT01499108: Time Course of the Blood Pressure Lowering Effect of Liraglutide Therapy in Type 2 Diabetes
Official title: Time Course of the Blood Pressure Lowering Effect of Liraglutide Therapy in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: type 2 diabetes
hypertension
liraglutide
kidney function
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2011-12-26
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Background: Preclinical blood pressure (BP) data from studies of hypoglycemic effects of liraglutide treatment (the LEAD program), revealed a significant antihypertensive potential. The time course and the mechanism behind this effect are unknown.

Objectives: To evaluate the time course of the antihypertensive effect of liraglutide treatment in patients with type 2 diabetes

Design: Open-label study with intervention and subsequent washout period

Patient Population: 35 hypertensive (SBP ≥130 mm Hg and DBP ≥80 mmHg) patients with type 2 diabetes.

Intervention: All patients will be treated with liraglutide 0.6 mg once daily for 7 days and will then be titrated to 1.2 mg once daily for 14 days and then titrated to 1.8 mg once daily for 4 weeks. This is followed by a washout period of 3 weeks without liraglutide treatment.

Endpoints: 24-hour blood pressure, natriuresis, extra cellular volume (ECV

Detailed description: Hypotheses Primary hypothesis • Liraglutide treatment causes a reduction in 24h BP

Secondary hypothesis:

* The effect on BP may be mediated by an increase in natriuresis, thereby affecting ECV
* The effect on BP may be mediated by a decrease in arterial stiffness and central aortic pressure

Purpose Primary purpose

• To assess how quickly the antihypertensive effect of liraglutide treatment set in after initiation in patients with type 2 diabetes

Secondary objectives

* To measure the effect of liraglutide treatment on natriuresis.
* To measure the effect of liraglutide treatment on ECV
* To measure the effect of liraglutide treatment on arterial stiffness
* To measure weight change after initiation of liraglutide treatment

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. Patients must be on treatment with metformin. Any form of treatment with SU compounds will be discontinued and washed out for two weeks prior to the start of study drug.
4. eGFR ≥ 60 ml/min/1.73 m2 (estimated by MDRD formula)
5. Fertile female patients must use chemical, hormonal and mechanical contraceptives or be in menopause (i.e. must not have had regular menstrual bleeding for at least one year) or have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least six months prior to screening
6. Patients must be on antihypertensive treatment or having elevated blood pressure (SBP ≥130 mm Hg and DBP ≥80 mmHg), lower than 170/105 mm Hg at baseline and the patients must be stable antihypertensive medication for at least 4 weeks prior to baseline
7. Patients must be on stable hypoglycemic medication for at least two weeks before the first visit.
8. Must be able to communicate with the investigator

Exclusion Criteria:

1. Ongoing insulin therapy
2. BP \> 170/105 mm Hg at baseline
3. Type 1 diabetes mellitus
4. Chronic pancreatitis / previous acute pancreatitis
5. Known or suspected hypersensitivity to trial product(s) or related products.
6. Treatment with oral glucocorticoids, calcineurin inhibitors, or dipeptidyl peptidase 4 (DPP4) inhibitors which in the Investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening
7. 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
8. Inflammatory bowel disease
9. 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
10. Previous bowel resection
11. Body mass index \<18.5 kg/m2
12. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
13. Clinical signs of diabetic gastroparesis
14. Impaired liver function (transaminases \> two times upper reference levels)

Primary outcomes:
measure: Change in ambulatory blood pressure
timeFrame: 50 days
Secondary outcomes:
measure: Change in ECV
timeFrame: 50 days
measure: Washout analysis
timeFrame: 21
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center
Study officials:
affiliation: Steno Diabetes Centes
name: Peter Rossing, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: von Scholten BJ, Hansen TW, Goetze JP, Persson F, Rossing P. Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes. J Diabetes Complications. 2015 Jul;29(5):670-4. doi: 10.1016/j.jdiacomp.2015.04.004. Epub 2015 Apr 11.