PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients
Objective: PB-119, a PEGylated exenatide injection, is a once-weekly glucagon-like peptide-1 receptor agonist. In the present study, we aimed to evaluate the effects of PB-119 on insulin resistance and beta-cell function in Chinese patients with type 2 diabetes mellitus (T2DM) to uncover its antidia...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1088670/full |
| _version_ | 1797685330451628032 |
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| author | Xu Liu Xu Liu Xu Liu Ling Song Ling Song Ling Song Yuanhui Zhang Haiyan Li Haiyan Li Haiyan Li Cheng Cui Cheng Cui Cheng Cui Dongyang Liu Dongyang Liu Dongyang Liu |
| author_facet | Xu Liu Xu Liu Xu Liu Ling Song Ling Song Ling Song Yuanhui Zhang Haiyan Li Haiyan Li Haiyan Li Cheng Cui Cheng Cui Cheng Cui Dongyang Liu Dongyang Liu Dongyang Liu |
| author_sort | Xu Liu |
| collection | DOAJ |
| description | Objective: PB-119, a PEGylated exenatide injection, is a once-weekly glucagon-like peptide-1 receptor agonist. In the present study, we aimed to evaluate the effects of PB-119 on insulin resistance and beta-cell function in Chinese patients with type 2 diabetes mellitus (T2DM) to uncover its antidiabetic characteristics.Methods: A total of 36 Chinese T2DM patients were randomized to receive 25 μg and 50 μg PB-119 once weekly and exenatide (5–10 μg injected under the skin 2 times a day adjusted by the doctor) for 12 weeks. Oral mixed meal tolerance tests were conducted before the study and on Day 79. The data were fitted to estimate beta-cell function and insulin sensitivity parameters using the SAAM II package integrating the oral minimal model (OMM), which was compared with Homeostatic Model Assessment (HOMA) analysis results.Results: Exenatide or PB-119 treatment, compared with their baseline, was associated with higher beta-cell function parameters (φb, φs and φtot), disposition index, insulin secretion rates, and a lower glucose area under the curve. High-dose PB-119 also has a higher insulin resistance parameter (SI) than the baseline, but HOMA-IR did not. For the homeostatic model assessment parameters, HOMA-IR showed no statistically significant changes within or between treatments. Only high-dose PB-119 improved HOMA-β after 12 weeks of treatment.Conclusion: After 12 weeks of treatment, PB-119 decreased glycemic levels by improving beta-cell function and insulin resistance. |
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| format | Article |
| id | doaj.art-d9e826f635994eb188db3ecb196c825f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-12T00:43:36Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d9e826f635994eb188db3ecb196c825f2023-09-15T01:27:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-09-011410.3389/fphar.2023.10886701088670PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patientsXu Liu0Xu Liu1Xu Liu2Ling Song3Ling Song4Ling Song5Yuanhui Zhang6Haiyan Li7Haiyan Li8Haiyan Li9Cheng Cui10Cheng Cui11Cheng Cui12Dongyang Liu13Dongyang Liu14Dongyang Liu15Drug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Cardiovascular Receptors Research, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Cardiovascular Receptors Research, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Cardiovascular Receptors Research, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Cardiovascular Receptors Research, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Cardiovascular Receptors Research, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaObjective: PB-119, a PEGylated exenatide injection, is a once-weekly glucagon-like peptide-1 receptor agonist. In the present study, we aimed to evaluate the effects of PB-119 on insulin resistance and beta-cell function in Chinese patients with type 2 diabetes mellitus (T2DM) to uncover its antidiabetic characteristics.Methods: A total of 36 Chinese T2DM patients were randomized to receive 25 μg and 50 μg PB-119 once weekly and exenatide (5–10 μg injected under the skin 2 times a day adjusted by the doctor) for 12 weeks. Oral mixed meal tolerance tests were conducted before the study and on Day 79. The data were fitted to estimate beta-cell function and insulin sensitivity parameters using the SAAM II package integrating the oral minimal model (OMM), which was compared with Homeostatic Model Assessment (HOMA) analysis results.Results: Exenatide or PB-119 treatment, compared with their baseline, was associated with higher beta-cell function parameters (φb, φs and φtot), disposition index, insulin secretion rates, and a lower glucose area under the curve. High-dose PB-119 also has a higher insulin resistance parameter (SI) than the baseline, but HOMA-IR did not. For the homeostatic model assessment parameters, HOMA-IR showed no statistically significant changes within or between treatments. Only high-dose PB-119 improved HOMA-β after 12 weeks of treatment.Conclusion: After 12 weeks of treatment, PB-119 decreased glycemic levels by improving beta-cell function and insulin resistance.https://www.frontiersin.org/articles/10.3389/fphar.2023.1088670/fullPB-119beta-cell functioninsulin resistanceoral minimal modeltype 2 diabetes |
| spellingShingle | Xu Liu Xu Liu Xu Liu Ling Song Ling Song Ling Song Yuanhui Zhang Haiyan Li Haiyan Li Haiyan Li Cheng Cui Cheng Cui Cheng Cui Dongyang Liu Dongyang Liu Dongyang Liu PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients Frontiers in Pharmacology PB-119 beta-cell function insulin resistance oral minimal model type 2 diabetes |
| title | PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients |
| title_full | PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients |
| title_fullStr | PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients |
| title_full_unstemmed | PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients |
| title_short | PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients |
| title_sort | pegylated exenatide injection pb 119 improves beta cell function and insulin resistance in treatment naive type 2 diabetes mellitus patients |
| topic | PB-119 beta-cell function insulin resistance oral minimal model type 2 diabetes |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1088670/full |
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