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A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes
INTRODUCTION: To investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Chinese patients with type 2 diabetes (T2D). METHODS: In this phase 1, double-blind, placebo-controlled, multiple dose study, patients were randomized into one of two cohorts to...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329955/ https://www.ncbi.nlm.nih.gov/pubmed/37285081 http://dx.doi.org/10.1007/s12325-023-02536-8 |
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author | Feng, Ping Sheng, Xiaoyan Ji, Yongjia Urva, Shweta Wang, Feng Miller, Sheila Qian, Chenxi An, Zhenmei Cui, Yimin |
author_facet | Feng, Ping Sheng, Xiaoyan Ji, Yongjia Urva, Shweta Wang, Feng Miller, Sheila Qian, Chenxi An, Zhenmei Cui, Yimin |
author_sort | Feng, Ping |
collection | PubMed |
description | INTRODUCTION: To investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Chinese patients with type 2 diabetes (T2D). METHODS: In this phase 1, double-blind, placebo-controlled, multiple dose study, patients were randomized into one of two cohorts to receive once-weekly subcutaneous tirzepatide or placebo. The initial tirzepatide dose in both cohorts was 2.5 mg, which was increased by 2.5 mg every 4 weeks to a maximum final dose of 10.0 mg at week 16 (Cohort 1) or 15.0 mg at week 24 (Cohort 2). The primary outcome was the safety and tolerability of tirzepatide. RESULTS: Twenty-four patients were randomized (tirzepatide 2.5–10.0 mg: n = 10, tirzepatide 2.5–15.0 mg: n = 10, placebo: n = 4); 22 completed the study. The most frequently reported treatment-emergent adverse events (TEAEs) among patients receiving tirzepatide were diarrhea and decreased appetite; most TEAEs were mild and resolved spontaneously with no serious adverse events reported in the tirzepatide groups and one in the placebo group. The plasma concentration half-life of tirzepatide was approximately 5–6 days. Mean glycated hemoglobin (HbA1c) decreased over time from baseline in the 2.5–10.0 mg (− 2.4%) and 2.5–15.0 mg (− 1.6%) tirzepatide groups, at week 16 and week 24, respectively, but remained steady in patients receiving placebo. Body weight decreased from baseline by − 4.2 kg at week 16 in the tirzepatide 2.5–10.0 mg group and by − 6.7 kg at week 24 in the 2.5–15.0 mg group. Mean fasting plasma glucose levels fell from baseline by − 4.6 mmol/L in the tirzepatide 2.5–10.0 mg group at week 16 and by − 3.7 mmol/L at week 24 in the tirzepatide 2.5–15.0 mg group. CONCLUSIONS: Tirzepatide was well tolerated in this population of Chinese patients with T2D. The safety, tolerability, PK, and PD profile of tirzepatide support once-weekly dosing in this population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04235959. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12325-023-02536-8. |
format | Online Article Text |
id | pubmed-10329955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-103299552023-07-11 A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes Feng, Ping Sheng, Xiaoyan Ji, Yongjia Urva, Shweta Wang, Feng Miller, Sheila Qian, Chenxi An, Zhenmei Cui, Yimin Adv Ther Original Research INTRODUCTION: To investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Chinese patients with type 2 diabetes (T2D). METHODS: In this phase 1, double-blind, placebo-controlled, multiple dose study, patients were randomized into one of two cohorts to receive once-weekly subcutaneous tirzepatide or placebo. The initial tirzepatide dose in both cohorts was 2.5 mg, which was increased by 2.5 mg every 4 weeks to a maximum final dose of 10.0 mg at week 16 (Cohort 1) or 15.0 mg at week 24 (Cohort 2). The primary outcome was the safety and tolerability of tirzepatide. RESULTS: Twenty-four patients were randomized (tirzepatide 2.5–10.0 mg: n = 10, tirzepatide 2.5–15.0 mg: n = 10, placebo: n = 4); 22 completed the study. The most frequently reported treatment-emergent adverse events (TEAEs) among patients receiving tirzepatide were diarrhea and decreased appetite; most TEAEs were mild and resolved spontaneously with no serious adverse events reported in the tirzepatide groups and one in the placebo group. The plasma concentration half-life of tirzepatide was approximately 5–6 days. Mean glycated hemoglobin (HbA1c) decreased over time from baseline in the 2.5–10.0 mg (− 2.4%) and 2.5–15.0 mg (− 1.6%) tirzepatide groups, at week 16 and week 24, respectively, but remained steady in patients receiving placebo. Body weight decreased from baseline by − 4.2 kg at week 16 in the tirzepatide 2.5–10.0 mg group and by − 6.7 kg at week 24 in the 2.5–15.0 mg group. Mean fasting plasma glucose levels fell from baseline by − 4.6 mmol/L in the tirzepatide 2.5–10.0 mg group at week 16 and by − 3.7 mmol/L at week 24 in the tirzepatide 2.5–15.0 mg group. CONCLUSIONS: Tirzepatide was well tolerated in this population of Chinese patients with T2D. The safety, tolerability, PK, and PD profile of tirzepatide support once-weekly dosing in this population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04235959. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12325-023-02536-8. Springer Healthcare 2023-06-07 2023 /pmc/articles/PMC10329955/ /pubmed/37285081 http://dx.doi.org/10.1007/s12325-023-02536-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Feng, Ping Sheng, Xiaoyan Ji, Yongjia Urva, Shweta Wang, Feng Miller, Sheila Qian, Chenxi An, Zhenmei Cui, Yimin A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes |
title | A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes |
title_full | A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes |
title_fullStr | A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes |
title_full_unstemmed | A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes |
title_short | A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes |
title_sort | phase 1 multiple dose study of tirzepatide in chinese patients with type 2 diabetes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329955/ https://www.ncbi.nlm.nih.gov/pubmed/37285081 http://dx.doi.org/10.1007/s12325-023-02536-8 |
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