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Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for treatment of type 2 diabetes mellitus; however, there have been concerns that GLP-1RA treatment may be associated with an increased incidence of pancreatitis. This study aimed to evaluate the incidence of pancreat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612359/ https://www.ncbi.nlm.nih.gov/pubmed/31077072 http://dx.doi.org/10.1007/s13300-019-0627-1 |
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author | Vetter, Marion L. Johnsson, Kristina Hardy, Elise Wang, Hui Iqbal, Nayyar |
author_facet | Vetter, Marion L. Johnsson, Kristina Hardy, Elise Wang, Hui Iqbal, Nayyar |
author_sort | Vetter, Marion L. |
collection | PubMed |
description | INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for treatment of type 2 diabetes mellitus; however, there have been concerns that GLP-1RA treatment may be associated with an increased incidence of pancreatitis. This study aimed to evaluate the incidence of pancreatitis in a pooled population of type 2 diabetes trials from the clinical development program of the GLP-1RA exenatide as well as to describe patient-level data for all reported cases. METHODS: The primary analysis examined pooled data among patients with type 2 diabetes from the controlled arms of 35 trials (ranging from 4 to 234 weeks’ duration) in the integrated clinical databases for exenatide twice daily, once weekly, and once-weekly suspension, excluding comparator arms with other incretin-based therapies. The exposure-adjusted incidence rate (EAIR) of pancreatitis was calculated for exenatide and non-exenatide (non-incretin-based therapy or placebo) treatment groups. Patient-level data were described for all pancreatitis incidences. RESULTS: The primary analysis included 5596 patients who received exenatide and 4462 in the non-exenatide group. The mean duration of study medication exposure for the exenatide and non-exenatide treatment groups was 57.0 and 47.9 weeks, respectively. Pancreatitis was diagnosed in 14 patients (exenatide, n = 8; non-exenatide, n = 6), of whom 13 recovered with or without sequelae. The pancreatitis EAIR was 0.1195 events per 100 patient-years [95% confidence interval (CI), 0.0516–0.2154] in the exenatide group versus 0.1276 events per 100 patient-years (95% CI 0.0468–0.2482) in the non-exenatide treatment group. The EAIR ratio for the exenatide versus non-exenatide treatment group was 0.761 (95% CI 0.231–2.510). CONCLUSION: In this pooled analysis of 10,058 patients among studies comparing exenatide with other glucose-lowering medications or placebo, pancreatitis was rare. The EAIRs of pancreatitis were low and similar between exenatide and non-exenatide treatment groups. No evidence of an association between exenatide and pancreatitis was observed. FUNDING: Bristol-Myers Squibb and AstraZeneca. PLAIN LANGUAGE SUMMARY: Plain language summary available for this article. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-019-0627-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6612359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-66123592019-07-23 Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials Vetter, Marion L. Johnsson, Kristina Hardy, Elise Wang, Hui Iqbal, Nayyar Diabetes Ther Original Research INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for treatment of type 2 diabetes mellitus; however, there have been concerns that GLP-1RA treatment may be associated with an increased incidence of pancreatitis. This study aimed to evaluate the incidence of pancreatitis in a pooled population of type 2 diabetes trials from the clinical development program of the GLP-1RA exenatide as well as to describe patient-level data for all reported cases. METHODS: The primary analysis examined pooled data among patients with type 2 diabetes from the controlled arms of 35 trials (ranging from 4 to 234 weeks’ duration) in the integrated clinical databases for exenatide twice daily, once weekly, and once-weekly suspension, excluding comparator arms with other incretin-based therapies. The exposure-adjusted incidence rate (EAIR) of pancreatitis was calculated for exenatide and non-exenatide (non-incretin-based therapy or placebo) treatment groups. Patient-level data were described for all pancreatitis incidences. RESULTS: The primary analysis included 5596 patients who received exenatide and 4462 in the non-exenatide group. The mean duration of study medication exposure for the exenatide and non-exenatide treatment groups was 57.0 and 47.9 weeks, respectively. Pancreatitis was diagnosed in 14 patients (exenatide, n = 8; non-exenatide, n = 6), of whom 13 recovered with or without sequelae. The pancreatitis EAIR was 0.1195 events per 100 patient-years [95% confidence interval (CI), 0.0516–0.2154] in the exenatide group versus 0.1276 events per 100 patient-years (95% CI 0.0468–0.2482) in the non-exenatide treatment group. The EAIR ratio for the exenatide versus non-exenatide treatment group was 0.761 (95% CI 0.231–2.510). CONCLUSION: In this pooled analysis of 10,058 patients among studies comparing exenatide with other glucose-lowering medications or placebo, pancreatitis was rare. The EAIRs of pancreatitis were low and similar between exenatide and non-exenatide treatment groups. No evidence of an association between exenatide and pancreatitis was observed. FUNDING: Bristol-Myers Squibb and AstraZeneca. PLAIN LANGUAGE SUMMARY: Plain language summary available for this article. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-019-0627-1) contains supplementary material, which is available to authorized users. Springer Healthcare 2019-05-10 2019-08 /pmc/articles/PMC6612359/ /pubmed/31077072 http://dx.doi.org/10.1007/s13300-019-0627-1 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Vetter, Marion L. Johnsson, Kristina Hardy, Elise Wang, Hui Iqbal, Nayyar Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials |
title | Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials |
title_full | Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials |
title_fullStr | Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials |
title_full_unstemmed | Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials |
title_short | Pancreatitis Incidence in the Exenatide BID, Exenatide QW, and Exenatide QW Suspension Development Programs: Pooled Analysis of 35 Clinical Trials |
title_sort | pancreatitis incidence in the exenatide bid, exenatide qw, and exenatide qw suspension development programs: pooled analysis of 35 clinical trials |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612359/ https://www.ncbi.nlm.nih.gov/pubmed/31077072 http://dx.doi.org/10.1007/s13300-019-0627-1 |
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