Purpose: The purpose of this study is to further study the mechanism by which liraglutide, a relatively new anti-hyperglycemic medication, might lower blood pressure in patients with Type 2 diabetes and high blood pressure.
Background: Type 2 diabetes is a worldwide health problem. As the reduction in blood pressure has been coupled to improvements in overall cardiovascular outcomes, the control of hypertension has become an important modifiable risk factor in the overall care of the patient with Type 2 Diabetes, in addition to glycemic control. Recently, several large-scale clinical trials evaluating the glucose-lowering effects of the anti-hyperglycemic agent, liraglutide (a glucagon-like peptide-1 receptor agonist), have demonstrated a modest yet persistent anti-hypertensive effect in patients with Type 2 diabetes. Study Objectives: Accordingly, the goal of this small study is to understand whether the blood pressure lowering effect of liraglutide is coupled to the release of vasoactive mediators which may stimulate natriuresis and/or diuresis and lower systolic blood pressure. Study Design: Randomized, double-masked, cross-over study with treatment of liraglutide or placebo for 3 weeks, with an intervening washout period for 3 weeks, and cross-over to identical treatment with placebo or liraglutide for 3 weeks. Study Patients: 20 patients with Type 2 Diabetes and Systolic Hypertension Endpoints: Change in vasoactive hormones, 24-hour ambulatory blood pressure, urinary sodium excretion patterns.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
22
Single cross-over study, 1 arm starting with liraglutide for 3 weeks crossed-over to placebo for 3 weeks, and 1 arm starting with placebo with cross-over to liraglutide for 3 weeks.
Single cross-over study, 1 arm starting with liraglutide for 3 weeks crossed-over to placebo for 3 weeks, and 1 arm starting with placebo with cross-over to liraglutide for 3 weeks.
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Canada
Toronto, Ontario, Canada
Change in plasma ANP level at 1 Day
+16.72 pg/mL, P = 0.24, 95% CI \[-12.1, +45.5\] at 2 hours
Time frame: Change from Baseline compared in plasma ANP following 1 dose of liraglutide (0.6 mg) compared to crossover treatment with placebo at the 2-hour timepoint
Change in plasma ANP level at 21 Days
-17.42 pg/mL, 95% CI \[-36.0, +1.21\] at 2 hours
Time frame: Change from Baseline in plasma ANP following 21 days of liraglutide (titrated to 1.8 mg) compared to crossover treatment with placebo at the 2-hour timepoint
Change in mean 24-Hr urinary sodium excretion rate following 21 days of liraglutide (titrated 1.8mg) compared to crossover with placebo (baseline-subtracted)
median change +14.18 mmol/L liraglutide vs. placebo (statistically significant, Wilcoxon rank sum)
Time frame: 21 days
Change in mean Nighttime urinary sodium excretion rate following 21 days of liraglutide (titrated 1.8mg) compared to crossover with placebo (baseline-subtracted)
median change +4.24 mmol/L nighttime, liraglutide vs. placebo (statistically significant, Wilcoxon Rank Sum)
Time frame: 21 days
Change in mean 24-Hr systolic BP, liraglutide compared to crossover with placebo (baseline-subtracted)
+2.33 ± 1.67, p=0.18;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Time frame: 21 days
Change in mean 24-hr diastolic BP, liraglutide compared to crossover with placebo (baseline-subtracted)
+3.78 ± 1.34, p=0.01;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Time frame: 21 days
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Change in mean 24-hr HR, liraglutide compared to crossover with placebo (baseline-subtracted)
+5.21 ± 2.42, p=0.05; Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Time frame: 21 days
Office-measured systolic BP; Treatment difference for liraglutide compared to crossover with placebo
-2.35 mmHg (3.49), p=0.51;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Time frame: 21 days
Office-measured diastolic BP;Treatment difference for liraglutide compared to crossover with placebo
+3.6 mmHg (2.33), p=0.14;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Time frame: 21 days
Office-measured heart rate;Treatment difference for liraglutide compared to crossover with placebo
+9.25 (3.51), p=0.02;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Time frame: 21 days