Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study

Abstract

BackgroundCardiovascular effects of glucose-lowering agents are of increasing interest. Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate (HR) and blood pressure (BP) in subjects with type 2 diabetes mellitus (T2DM).MethodsIn this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 μg for 4 weeks followed by 10 μg) or placebo BID for 12 weeks. Heart rate and BP were assessed with 24-hour ambulatory BP monitoring. The primary measure was change from baseline in mean 24-hour HR.ResultsFifty-four subjects (28 exenatide, 26 placebo) were randomized and comprised the intent-to-treat population. Baseline values (exenatide and placebo) were (mean ± SE) 74.4 ± 2.1 and 74.5 ± 1.9 beats/minute for HR, 126.4 ± 3.2 and 119.9 ± 2.8 mm Hg for systolic BP (SBP), and 75.2 ± 2.1 and 70.5 ± 2.0 mm Hg for diastolic BP (DBP). At 12 weeks, no significant change from baseline in 24-hour HR was observed with exenatide or placebo (LS mean ± SE, 2.1 ± 1.4 versus -0.7 ± 1.4 beats/minute, respectively; between treatments, p = 0.16). Exenatide therapy was associated with trends toward lower 24-hour, daytime, and nighttime SBP; changes in DBP were similar between groups. No changes in daytime or nighttime rate pressure product were observed. With exenatide, body weight decreased from baseline by -1.8 ± 0.4 kg (p < 0.0001; treatment difference -1.5 ± 0.6 kg, p < 0.05). The most frequently reported adverse event with exenatide was mild to moderate nausea.ConclusionsExenatide demonstrated no clinically meaningful effects on HR over 12 weeks of treatment in subjects with T2DM. The observed trends toward lower SBP with exenatide warrant future investigation.Trial registrationNCT00516074

Liraglutide Promotes Natriuresis but Does Not Increase Circulating Levels of Atrial Natriuretic Peptide in Hypertensive Subjects With Type 2 Diabetes

“…These limitations may partially explain why we were unable to detect significant changes in plasma ANP levels or SBP in this patient population. Nevertheless, our BP findings are in agreement with the results of a trial examining the BP-lowering effects of twice-daily exenatide, which reported trends toward lowering of SBP, daytime DBP, and nighttime BP; however, none of the differences reported were statistically significant (19). In contrast, Ferdinand et al (20) randomized 755 patients to dulaglutide or placebo and reported a significant reduction in SBP after 16 weeks in 251 subjects randomized to receive 1.5 mg of dulaglutide administered once weekly.…”

Adverse Effects of GLP-1 Receptor Agonists

“…Exenatide, liraglutide, and albiglutide do not cause any clinically relevant increase in the QTc interval [98][99][100][101]. Exenatide does not prolong QTc even at supratherapeutic concentrations [102].…”

GLP-1, the Gut-Brain, and Brain-Periphery Axes

“…Although a 48 hour continuous subcutaneous GLP-1 infusion has no chronotropic effect, it can decrease both systolic and diastolic blood pressure in patients [104]. Interestingly, the same observations are reported in long-term studies (12 weeks to 6 months) with exenatide [105][106]. However, in non-diabetic patients with congestive heart failure, a minor increase in heart rate and diastolic blood pressure was observed during a 48 hour continuous subcutaneous GLP-1 infusion [107].…”