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Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial
INTRODUCTION: Dulaglutide is a recombinant glucagon-like peptide-1 immunoglobulin G4 Fc fusion protein approved for treating patients with type 2 diabetes (T2D). The aim of this study was to assess postprandial data over 4 weeks for dulaglutide (0.75 mg) versus placebo after a standardized test meal...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531535/ https://www.ncbi.nlm.nih.gov/pubmed/30949907 http://dx.doi.org/10.1007/s13300-019-0605-7 |
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author | Inoue, Megumi Shiramoto, Masanari Oura, Tomonori Nasu, Risa Nakano, Masako Takeuchi, Masakazu |
author_facet | Inoue, Megumi Shiramoto, Masanari Oura, Tomonori Nasu, Risa Nakano, Masako Takeuchi, Masakazu |
author_sort | Inoue, Megumi |
collection | PubMed |
description | INTRODUCTION: Dulaglutide is a recombinant glucagon-like peptide-1 immunoglobulin G4 Fc fusion protein approved for treating patients with type 2 diabetes (T2D). The aim of this study was to assess postprandial data over 4 weeks for dulaglutide (0.75 mg) versus placebo after a standardized test meal in Japanese patients with T2D. METHODS: The pharmacodynamic (PD) effects of once-weekly dulaglutide (0.75 mg) in Japanese patients with T2D on diet and exercise therapy (N = 12) were evaluated by assessing postprandial data up to week 4 in a phase 4, single-center, randomized, cross-over, single-blind, placebo-controlled study. The primary end point was the change in 4-h glucose area under the concentration versus time curve [AUC (0–4 h)] from baseline to week 4. Secondary end points included changes from baseline in other PD parameters (insulin, C-peptide, glucagon, and triglycerides) at weeks 1, 2, and 4 and the safety and tolerability of dulaglutide 0.75 mg. Continuous glucose monitoring (CGM) during the 1st week was performed as an exploratory measure in each treatment period. RESULTS: The decrease in AUC (0–4 h) from baseline to week 4 following dulaglutide administration was statistically significant compared with placebo at weeks 1, 2, and 4 (P < 0.0001). Insulin and C-peptide levels were also significantly increased (P < 0.05) with dulaglutide versus placebo at weeks 2 and 4. There were no statistically significant differences between groups in glucagon and triglyceride levels. Daily average glucose concentrations were decreased on the day after the first administration of dulaglutide and remained at similar levels for 4 days. The incidence of treatment-emergent adverse events was slightly higher with dulaglutide versus placebo. CONCLUSION: In conclusion, dulaglutide decreased postprandial glucose from week 1 in Japanese patients with T2D, indicating that dulaglutide treatment is associated with favorable PD effects soon after treatment begins. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03315780. FUNDING: Eli Lilly Japan K.K. (Kobe, Japan). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-019-0605-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6531535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-65315352019-06-07 Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial Inoue, Megumi Shiramoto, Masanari Oura, Tomonori Nasu, Risa Nakano, Masako Takeuchi, Masakazu Diabetes Ther Original Research INTRODUCTION: Dulaglutide is a recombinant glucagon-like peptide-1 immunoglobulin G4 Fc fusion protein approved for treating patients with type 2 diabetes (T2D). The aim of this study was to assess postprandial data over 4 weeks for dulaglutide (0.75 mg) versus placebo after a standardized test meal in Japanese patients with T2D. METHODS: The pharmacodynamic (PD) effects of once-weekly dulaglutide (0.75 mg) in Japanese patients with T2D on diet and exercise therapy (N = 12) were evaluated by assessing postprandial data up to week 4 in a phase 4, single-center, randomized, cross-over, single-blind, placebo-controlled study. The primary end point was the change in 4-h glucose area under the concentration versus time curve [AUC (0–4 h)] from baseline to week 4. Secondary end points included changes from baseline in other PD parameters (insulin, C-peptide, glucagon, and triglycerides) at weeks 1, 2, and 4 and the safety and tolerability of dulaglutide 0.75 mg. Continuous glucose monitoring (CGM) during the 1st week was performed as an exploratory measure in each treatment period. RESULTS: The decrease in AUC (0–4 h) from baseline to week 4 following dulaglutide administration was statistically significant compared with placebo at weeks 1, 2, and 4 (P < 0.0001). Insulin and C-peptide levels were also significantly increased (P < 0.05) with dulaglutide versus placebo at weeks 2 and 4. There were no statistically significant differences between groups in glucagon and triglyceride levels. Daily average glucose concentrations were decreased on the day after the first administration of dulaglutide and remained at similar levels for 4 days. The incidence of treatment-emergent adverse events was slightly higher with dulaglutide versus placebo. CONCLUSION: In conclusion, dulaglutide decreased postprandial glucose from week 1 in Japanese patients with T2D, indicating that dulaglutide treatment is associated with favorable PD effects soon after treatment begins. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03315780. FUNDING: Eli Lilly Japan K.K. (Kobe, Japan). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-019-0605-7) contains supplementary material, which is available to authorized users. Springer Healthcare 2019-04-04 2019-06 /pmc/articles/PMC6531535/ /pubmed/30949907 http://dx.doi.org/10.1007/s13300-019-0605-7 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 Inoue, Megumi Shiramoto, Masanari Oura, Tomonori Nasu, Risa Nakano, Masako Takeuchi, Masakazu Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial |
title | Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial |
title_full | Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial |
title_fullStr | Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial |
title_full_unstemmed | Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial |
title_short | Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial |
title_sort | effect of once-weekly dulaglutide on glucose levels in japanese patients with type 2 diabetes: findings from a phase 4, randomized controlled trial |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531535/ https://www.ncbi.nlm.nih.gov/pubmed/30949907 http://dx.doi.org/10.1007/s13300-019-0605-7 |
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