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


METHODS
In this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 microg for 4 weeks followed by 10 microg) 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.


RESULTS
Fifty-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.


CONCLUSIONS
Exenatide 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.


BACKGROUND
NCT00516074.
Gill
Anne
A
Eli Lilly and Company, Indianapolis, USA.
Hoogwerf
Byron J
BJ
Burger
Jude
J
Bruce
Simon
S
Macconell
Leigh
L
Yan
Ping
P
Braun
Daniel
D
Giaconia
Joseph
J
Malone
James
J
D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004311:Double-Blind Method; D000077270:Exenatide; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018670:Monitoring, Ambulatory; D010455:Peptides / Q000494:pharmacology*; D010865:Pilot Projects; D010919:Placebos; D014688:Venoms / Q000494:pharmacology*
D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D010919:Placebos; D014688:Venoms