TY - JOUR
T1 - Changes in Heart Rate Associated with Exenatide Once Weekly
T2 - Pooled Analysis of Clinical Data in Patients with Type 2 Diabetes
AU - Marso, Steven P.
AU - Hardy, Elise
AU - Han, Jenny
AU - Wang, Hui
AU - Chilton, Robert J.
N1 - Funding Information:
Disclosures. Steven P. Marso has received significant research grants from Amylin Pharmaceuticals, Novo Nordisk, Terumo, The Medicines Company, and Volcano Corporation, has been on a speakers bureau for Novo Nordisk, and has consulted for Novo Nordisk and St. Jude Medical. Elise Hardy is an employee of AstraZeneca. Jenny Han was an employee of Bristol-Myers Squibb/AstraZeneca at the time of the study. Hui Wang is a consultant of Astra-Zeneca. Robert J. Chilton has received modest research grants from the National Institutes of Health, research support from Takeda, and has been a consultant or part of an advisory board for Bristol-Myers Squibb, Eli Lilly & Company, Merck Sharp & Dohme, Pfizer, and Takeda.
Funding Information:
ing support was provided by Raewyn M. Poole of inScience Communications, Springer Healthcare (Philadelphia, PA, USA), and funded by AstraZeneca. Leigh A. MacConell, PhD, who was an employee of Bristol-Myers Squibb/As-traZeneca at the time the study was conducted, supported initiation of this project and provided critical review of initial drafts. Mary Beth DeYoung, PhD, and Peter Öhman, MD, PhD, of AstraZeneca, contributed to the review of this manuscript.
Funding Information:
Funding. This analysis was supported by AstraZeneca and Bristol-Myers Squibb. The authors were responsible for data interpretation. AstraZeneca provided funding for medical writing support and article processing fees, and employees of AstraZeneca contributed to the review of this manuscript.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. Methods: A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10–30 weeks’ duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups). The time course and size of heart rate changes from baseline and the relationship of heart rate change with baseline heart rate were studied. A multivariate analysis (9 studies; N = 3903) examined associations between patient characteristics or treatments and heart rate increases. Results: Mean baseline heart rate ± standard deviation was 75.0 ± 8.5 beats per minute (bpm) with exenatide QW (n = 2096), 75.8 ± 8.7 bpm with exenatide BID (n = 606), 75.2 ± 8.9 bpm with liraglutide (n = 450), and 74.5 ± 8.6 bpm with non-GLP-1RAs (n = 1443). Least-squares mean ± standard error changes from baseline to final heart rate were + 2.7 ± 0.2, + 1.0 ± 0.3, and + 3.0 ± 0.4 bpm with exenatide QW, exenatide BID, and liraglutide, respectively, and − 0.8 ± 0.2 bpm with non-GLP-1RAs. The size and direction of heart rate changes in individual patients varied within each treatment group at all time points. At posttreatment follow-up, heart rate reverted to the baseline level after GLP-1RA discontinuation. Heart rate changes correlated negatively with baseline heart rate for all therapies (r = − 0.3 to − 0.4). Baseline heart rate was the strongest predictor of increased heart rate. Conclusions: Small increases in heart rate were associated with exenatide QW, exenatide BID, and liraglutide treatments but reverted to baseline after discontinuation. Increases were more likely in patients with a low baseline heart rate. The clinical relevance of these heart rate increases is unknown but will be clarified by several ongoing and recently completed cardiovascular outcome studies.
AB - Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. Methods: A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10–30 weeks’ duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups). The time course and size of heart rate changes from baseline and the relationship of heart rate change with baseline heart rate were studied. A multivariate analysis (9 studies; N = 3903) examined associations between patient characteristics or treatments and heart rate increases. Results: Mean baseline heart rate ± standard deviation was 75.0 ± 8.5 beats per minute (bpm) with exenatide QW (n = 2096), 75.8 ± 8.7 bpm with exenatide BID (n = 606), 75.2 ± 8.9 bpm with liraglutide (n = 450), and 74.5 ± 8.6 bpm with non-GLP-1RAs (n = 1443). Least-squares mean ± standard error changes from baseline to final heart rate were + 2.7 ± 0.2, + 1.0 ± 0.3, and + 3.0 ± 0.4 bpm with exenatide QW, exenatide BID, and liraglutide, respectively, and − 0.8 ± 0.2 bpm with non-GLP-1RAs. The size and direction of heart rate changes in individual patients varied within each treatment group at all time points. At posttreatment follow-up, heart rate reverted to the baseline level after GLP-1RA discontinuation. Heart rate changes correlated negatively with baseline heart rate for all therapies (r = − 0.3 to − 0.4). Baseline heart rate was the strongest predictor of increased heart rate. Conclusions: Small increases in heart rate were associated with exenatide QW, exenatide BID, and liraglutide treatments but reverted to baseline after discontinuation. Increases were more likely in patients with a low baseline heart rate. The clinical relevance of these heart rate increases is unknown but will be clarified by several ongoing and recently completed cardiovascular outcome studies.
KW - Exenatide once weekly
KW - Glucagon-like peptide-1 receptor agonists
KW - Heart rate
KW - Tolerability
KW - Type 2 diabetes
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U2 - 10.1007/s13300-018-0370-z
DO - 10.1007/s13300-018-0370-z
M3 - Article
C2 - 29397532
AN - SCOPUS:85044520003
VL - 9
SP - 551
EP - 564
JO - Diabetes Therapy
JF - Diabetes Therapy
SN - 1869-6953
IS - 2
ER -