Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials

Leigh MacConell, Carl Brown, Kate Gurney, Jenny HanAmylin Pharmaceuticals, Inc. San Diego, CA, USABackground: Exenatide twice daily is a first-in-class glucagon-like peptide receptor agonist approved for the treatment of type 2 diabetes. The objective of this analysis was to evaluate the safety prof...

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Autores principales:	Gurney K, Brown C, MacConell L, Han J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/fd89b9880170477489a05b4961494654
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spelling	oai:doaj.org-article:fd89b9880170477489a05b49614946542021-12-02T01:51:43ZSafety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials1178-7007https://doaj.org/article/fd89b9880170477489a05b49614946542012-02-01T00:00:00Zhttp://www.dovepress.com/safety-and-tolerability-of-exenatide-twice-daily-in-patients-with-type-a9298https://doaj.org/toc/1178-7007Leigh MacConell, Carl Brown, Kate Gurney, Jenny HanAmylin Pharmaceuticals, Inc. San Diego, CA, USABackground: Exenatide twice daily is a first-in-class glucagon-like peptide receptor agonist approved for the treatment of type 2 diabetes. The objective of this analysis was to evaluate the safety profile of exenatide twice daily and to compare its profile with that of a pooled comparator (placebo and insulin) in patients with type 2 diabetes.Methods: Data from 19 completed, randomized, controlled clinical trials of exenatide twice daily (5 &micro;g and 10 &micro;g) were pooled and analyzed; the pooled data included 5594 intent-to-treat patients who were followed for 12&ndash;52 weeks. Incidence rates, exposure-adjusted incidence rates, and 95% confidence intervals around risk differences between groups were calculated.Results: Baseline demographics and exposure time were comparable between groups (exenatide, N = 3261; pooled comparator, N = 2333; mean exposure time 166&ndash;171 days). Transient, mild-to-moderate nausea was the most frequent adverse event with exenatide (36.9% versus 8.3% in the pooled comparator). The incidence of hypoglycemia (minor or major) with concomitant sulfonylurea (exenatide 26.5%, pooled comparator 20.7%) was higher than that without sulfonylurea (exenatide 3.1%, pooled comparator 2.7%) in all groups. Serious adverse events, discontinuations due to serious adverse events, and deaths were reported with similar frequency in the exenatide and pooled comparator groups. Composite exposure-adjusted incidence rates were not statistically different between groups for pancreatitis, renal impairment, or major adverse cardiac events; there was a difference in incidence rates for benign thyroid neoplasm (0.3% versus 0%).Conclusion: Overall, this analysis, representing over 1500 patient-years of exposure, demonstrated that exenatide twice daily was safe and generally well tolerated in patients with type 2 diabetes. The incidence of most adverse events, including serious adverse events, was similar in both exenatide-treated and comparator-treated patients. The most distinct differences between groups were in gastrointestinal-related adverse events, which is consistent with other therapies within the glucagon-like peptide class.Keywords: exenatide, safety, adverse events, risk differenceGurney KBrown CMacConell LHan JDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2012, Iss default, Pp 29-41 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Gurney K Brown C MacConell L Han J Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials
description	Leigh MacConell, Carl Brown, Kate Gurney, Jenny HanAmylin Pharmaceuticals, Inc. San Diego, CA, USABackground: Exenatide twice daily is a first-in-class glucagon-like peptide receptor agonist approved for the treatment of type 2 diabetes. The objective of this analysis was to evaluate the safety profile of exenatide twice daily and to compare its profile with that of a pooled comparator (placebo and insulin) in patients with type 2 diabetes.Methods: Data from 19 completed, randomized, controlled clinical trials of exenatide twice daily (5 &micro;g and 10 &micro;g) were pooled and analyzed; the pooled data included 5594 intent-to-treat patients who were followed for 12&ndash;52 weeks. Incidence rates, exposure-adjusted incidence rates, and 95% confidence intervals around risk differences between groups were calculated.Results: Baseline demographics and exposure time were comparable between groups (exenatide, N = 3261; pooled comparator, N = 2333; mean exposure time 166&ndash;171 days). Transient, mild-to-moderate nausea was the most frequent adverse event with exenatide (36.9% versus 8.3% in the pooled comparator). The incidence of hypoglycemia (minor or major) with concomitant sulfonylurea (exenatide 26.5%, pooled comparator 20.7%) was higher than that without sulfonylurea (exenatide 3.1%, pooled comparator 2.7%) in all groups. Serious adverse events, discontinuations due to serious adverse events, and deaths were reported with similar frequency in the exenatide and pooled comparator groups. Composite exposure-adjusted incidence rates were not statistically different between groups for pancreatitis, renal impairment, or major adverse cardiac events; there was a difference in incidence rates for benign thyroid neoplasm (0.3% versus 0%).Conclusion: Overall, this analysis, representing over 1500 patient-years of exposure, demonstrated that exenatide twice daily was safe and generally well tolerated in patients with type 2 diabetes. The incidence of most adverse events, including serious adverse events, was similar in both exenatide-treated and comparator-treated patients. The most distinct differences between groups were in gastrointestinal-related adverse events, which is consistent with other therapies within the glucagon-like peptide class.Keywords: exenatide, safety, adverse events, risk difference
format	article
author	Gurney K Brown C MacConell L Han J
author_facet	Gurney K Brown C MacConell L Han J
author_sort	Gurney K
title	Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials
title_short	Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials
title_full	Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials
title_fullStr	Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials
title_full_unstemmed	Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials
title_sort	safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/fd89b9880170477489a05b4961494654
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Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials

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