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
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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Subcutaneous injection of liraglutide at doses of 0.6, 1.2, and 1.8 mg once daily during the 49 days duration of the study
Steno Diabetes Center
Gentofte Municipality, Denmark
Change in ambulatory blood pressure
Change in 24h BP from day 1 to day 49 (baseline to end of treatment) and time to statistically significant change in BP 24h after initiation of or increased dose of liraglutide
Time frame: 50 days
Change in ECV
Changes in ECV (measured by GFR), urinary sodium, weight, arterial stiffness and daily home-BP, from day 1 to day 49 (baseline to end of treatment).
Time frame: 50 days
Washout analysis
Change in 24h BP, ECV, weight, arterial stiffness from day 49 to day 70th
Time frame: 21
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