Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus
Background and Objectives Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of...
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| creator | Wang, Yitong Xu, Bingfeng Zhu, Lixia Lou, Kun Chen, Yingli Zhao, Xia Wang, Qian Xu, Ling Guo, Xiaohui Ji, Linong Cui, Yimin Fang, Yi |
| description | Background and Objectives
Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM).
Design and methods
In the randomized, open-label study, Chinese patients with T2DM (
n
= 36) were randomly assigned to three groups of rE-4 (
n
= 12), rE-4 with metformin (
n
= 12) and exenatide (
n
= 12, as the control group) for 12 weeks. rE-4 and exenatide were administered by subcutaneous injection in the abdomen, and metformin was given by oral administration. Patients received rE-4 or exenatide 5 μg twice a day for the first 4 weeks and adjusted the dose of rE-4 or exenatide to 10 μg twice a day at day 29 for the following 8 weeks, if their glycated albumin (GA) values were still greater than 17%. We evaluated pharmacokinetic parameters of rE-4 and exenatide, fasting plasma glucose (FPG), 2-h postprandial blood glucose (PG2 h), glycosylated hemoglobin (HbA1c) and body weight at designated time points.
Results
Thirty-six patients were enrolled, and 29 subjects finished the study. rE-4 was absorbed quickly with a median peak-reaching time (
t
max
) of 0.8–1.5 h and eliminated rapidly with a median terminal half-life (
t
1/2z
) of 1.6–1.9 h. The exposure of rE-4 increased in an approximately dose-proportional method without accumulation. rE-4 10 μg twice a day could reduce FPG (~2.29 mmol/L), PG2 h (~6.00 mmol/L), HbA1c (~1.19%) and body weight (~0.48 kg) from baseline to 12 weeks, with no statistical significance compared with exenatide (FPG: ~1.88 mmol/L; PG2 h: ~6.66 mmol/L; HbA1c: ~1.13%; body weight: ~0.47 kg) and rE-4 with metformin (FPG: ~2.33 mmol/L; PG2 h: ~6.51 mmol/L; HbA1c: ~0.84%; body weight: ~1.16 kg) (
p
> 0.05).
Conclusions
rE-4 twice a day has a pharmacokinetic profile similar to exenatide and rE-4 with metformin after single and multiple doses in Chinese patients with T2DM. Also, rE-4 could improve glycemic control effectively.
ClinicalTrials.gov identifier
NCT01342042. |
| doi_str_mv | 10.1007/s40261-017-0569-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1990423443</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1990423443</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-a6400d95e203785f250801bdaffaaba68ce0c274ea34ecd9df40c19af3e84bd73</originalsourceid><addsrcrecordid>eNp1kctuFDEQRS0EIiHwAWyQJTawMPjVDy-jIQSkiRhBWLfcdvWMk267sd1CwxfyWXgyCWLDqm6pTt2yfBF6yeg7RmnzPknKa0YoawitakXYI3TKWFOEYu3jOy0Ir2pxgp6ldEMpq1nNn6IT3irBlapO0e_NTsdJm3DrPGRnEtbe4k2E0U3O67jHD4Ddez0dgDDgb85vRyB37NUyZjeXzoYEeL0P886N7hdY_BVMmPri4jO-HBejt8GT0d0C3sCcnQXCDkzRIeLzMnQp4zfxgsi32Hm82pUnFcuNzg58Tvinyzt8vZ8Bc_zB6R4yJHwF4-jykp6jJ4MeE7y4r2fo-8eL69Unsv5y-Xl1viZGNDwTXUtKraqAU9G01cAr2lLWWz0MWve6bg1QwxsJWkgwVtlBUsOUHgS0sreNOEOvj75zDD8WSLm7CUv05WTHlKKSCylFodiRMjGkFGHo5uim8p0do90hu-6YXVey6w7ZdazsvLp3XvoJ7N-Nh7AKwI9AKiO_hfjP6f-6_gEwFqgQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1990423443</pqid></control><display><type>article</type><title>Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Wang, Yitong ; Xu, Bingfeng ; Zhu, Lixia ; Lou, Kun ; Chen, Yingli ; Zhao, Xia ; Wang, Qian ; Xu, Ling ; Guo, Xiaohui ; Ji, Linong ; Cui, Yimin ; Fang, Yi</creator><creatorcontrib>Wang, Yitong ; Xu, Bingfeng ; Zhu, Lixia ; Lou, Kun ; Chen, Yingli ; Zhao, Xia ; Wang, Qian ; Xu, Ling ; Guo, Xiaohui ; Ji, Linong ; Cui, Yimin ; Fang, Yi</creatorcontrib><description>Background and Objectives
Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM).
Design and methods
In the randomized, open-label study, Chinese patients with T2DM (
n
= 36) were randomly assigned to three groups of rE-4 (
n
= 12), rE-4 with metformin (
n
= 12) and exenatide (
n
= 12, as the control group) for 12 weeks. rE-4 and exenatide were administered by subcutaneous injection in the abdomen, and metformin was given by oral administration. Patients received rE-4 or exenatide 5 μg twice a day for the first 4 weeks and adjusted the dose of rE-4 or exenatide to 10 μg twice a day at day 29 for the following 8 weeks, if their glycated albumin (GA) values were still greater than 17%. We evaluated pharmacokinetic parameters of rE-4 and exenatide, fasting plasma glucose (FPG), 2-h postprandial blood glucose (PG2 h), glycosylated hemoglobin (HbA1c) and body weight at designated time points.
Results
Thirty-six patients were enrolled, and 29 subjects finished the study. rE-4 was absorbed quickly with a median peak-reaching time (
t
max
) of 0.8–1.5 h and eliminated rapidly with a median terminal half-life (
t
1/2z
) of 1.6–1.9 h. The exposure of rE-4 increased in an approximately dose-proportional method without accumulation. rE-4 10 μg twice a day could reduce FPG (~2.29 mmol/L), PG2 h (~6.00 mmol/L), HbA1c (~1.19%) and body weight (~0.48 kg) from baseline to 12 weeks, with no statistical significance compared with exenatide (FPG: ~1.88 mmol/L; PG2 h: ~6.66 mmol/L; HbA1c: ~1.13%; body weight: ~0.47 kg) and rE-4 with metformin (FPG: ~2.33 mmol/L; PG2 h: ~6.51 mmol/L; HbA1c: ~0.84%; body weight: ~1.16 kg) (
p
> 0.05).
Conclusions
rE-4 twice a day has a pharmacokinetic profile similar to exenatide and rE-4 with metformin after single and multiple doses in Chinese patients with T2DM. Also, rE-4 could improve glycemic control effectively.
ClinicalTrials.gov identifier
NCT01342042.</description><identifier>ISSN: 1173-2563</identifier><identifier>EISSN: 1179-1918</identifier><identifier>DOI: 10.1007/s40261-017-0569-1</identifier><identifier>PMID: 28932995</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adult ; Amino acids ; Asian Continental Ancestry Group ; Blood Glucose - drug effects ; Diabetes ; Diabetes Mellitus, Type 2 - drug therapy ; Drug dosages ; Fasting ; Female ; Glucagon-Like Peptide-1 Receptor - agonists ; Glucose ; Glycated Hemoglobin A - analysis ; Half-Life ; Hepatitis ; Humans ; Hypoglycemic Agents - administration & dosage ; Injections, Subcutaneous ; Insulin resistance ; Internal Medicine ; Male ; Medicine & Public Health ; Metformin - administration & dosage ; Middle Aged ; Original Research Article ; Peptides ; Peptides - administration & dosage ; Pharmaceutical sciences ; Pharmacodynamics ; Pharmacokinetics ; Pharmacology/Toxicology ; Pharmacotherapy ; Postprandial Period - drug effects ; Venoms - administration & dosage</subject><ispartof>Clinical drug investigation, 2017-12, Vol.37 (12), p.1107-1115</ispartof><rights>Springer International Publishing AG 2017</rights><rights>Copyright Springer Science & Business Media Dec 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-a6400d95e203785f250801bdaffaaba68ce0c274ea34ecd9df40c19af3e84bd73</citedby><cites>FETCH-LOGICAL-c372t-a6400d95e203785f250801bdaffaaba68ce0c274ea34ecd9df40c19af3e84bd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40261-017-0569-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40261-017-0569-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28932995$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yitong</creatorcontrib><creatorcontrib>Xu, Bingfeng</creatorcontrib><creatorcontrib>Zhu, Lixia</creatorcontrib><creatorcontrib>Lou, Kun</creatorcontrib><creatorcontrib>Chen, Yingli</creatorcontrib><creatorcontrib>Zhao, Xia</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Xu, Ling</creatorcontrib><creatorcontrib>Guo, Xiaohui</creatorcontrib><creatorcontrib>Ji, Linong</creatorcontrib><creatorcontrib>Cui, Yimin</creatorcontrib><creatorcontrib>Fang, Yi</creatorcontrib><title>Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus</title><title>Clinical drug investigation</title><addtitle>Clin Drug Investig</addtitle><addtitle>Clin Drug Investig</addtitle><description>Background and Objectives
Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM).
Design and methods
In the randomized, open-label study, Chinese patients with T2DM (
n
= 36) were randomly assigned to three groups of rE-4 (
n
= 12), rE-4 with metformin (
n
= 12) and exenatide (
n
= 12, as the control group) for 12 weeks. rE-4 and exenatide were administered by subcutaneous injection in the abdomen, and metformin was given by oral administration. Patients received rE-4 or exenatide 5 μg twice a day for the first 4 weeks and adjusted the dose of rE-4 or exenatide to 10 μg twice a day at day 29 for the following 8 weeks, if their glycated albumin (GA) values were still greater than 17%. We evaluated pharmacokinetic parameters of rE-4 and exenatide, fasting plasma glucose (FPG), 2-h postprandial blood glucose (PG2 h), glycosylated hemoglobin (HbA1c) and body weight at designated time points.
Results
Thirty-six patients were enrolled, and 29 subjects finished the study. rE-4 was absorbed quickly with a median peak-reaching time (
t
max
) of 0.8–1.5 h and eliminated rapidly with a median terminal half-life (
t
1/2z
) of 1.6–1.9 h. The exposure of rE-4 increased in an approximately dose-proportional method without accumulation. rE-4 10 μg twice a day could reduce FPG (~2.29 mmol/L), PG2 h (~6.00 mmol/L), HbA1c (~1.19%) and body weight (~0.48 kg) from baseline to 12 weeks, with no statistical significance compared with exenatide (FPG: ~1.88 mmol/L; PG2 h: ~6.66 mmol/L; HbA1c: ~1.13%; body weight: ~0.47 kg) and rE-4 with metformin (FPG: ~2.33 mmol/L; PG2 h: ~6.51 mmol/L; HbA1c: ~0.84%; body weight: ~1.16 kg) (
p
> 0.05).
Conclusions
rE-4 twice a day has a pharmacokinetic profile similar to exenatide and rE-4 with metformin after single and multiple doses in Chinese patients with T2DM. Also, rE-4 could improve glycemic control effectively.
ClinicalTrials.gov identifier
NCT01342042.</description><subject>Adult</subject><subject>Amino acids</subject><subject>Asian Continental Ancestry Group</subject><subject>Blood Glucose - drug effects</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Drug dosages</subject><subject>Fasting</subject><subject>Female</subject><subject>Glucagon-Like Peptide-1 Receptor - agonists</subject><subject>Glucose</subject><subject>Glycated Hemoglobin A - analysis</subject><subject>Half-Life</subject><subject>Hepatitis</subject><subject>Humans</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Injections, Subcutaneous</subject><subject>Insulin resistance</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine & Public Health</subject><subject>Metformin - administration & dosage</subject><subject>Middle Aged</subject><subject>Original Research Article</subject><subject>Peptides</subject><subject>Peptides - administration & dosage</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Postprandial Period - drug effects</subject><subject>Venoms - administration & dosage</subject><issn>1173-2563</issn><issn>1179-1918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kctuFDEQRS0EIiHwAWyQJTawMPjVDy-jIQSkiRhBWLfcdvWMk267sd1CwxfyWXgyCWLDqm6pTt2yfBF6yeg7RmnzPknKa0YoawitakXYI3TKWFOEYu3jOy0Ir2pxgp6ldEMpq1nNn6IT3irBlapO0e_NTsdJm3DrPGRnEtbe4k2E0U3O67jHD4Ddez0dgDDgb85vRyB37NUyZjeXzoYEeL0P886N7hdY_BVMmPri4jO-HBejt8GT0d0C3sCcnQXCDkzRIeLzMnQp4zfxgsi32Hm82pUnFcuNzg58Tvinyzt8vZ8Bc_zB6R4yJHwF4-jykp6jJ4MeE7y4r2fo-8eL69Unsv5y-Xl1viZGNDwTXUtKraqAU9G01cAr2lLWWz0MWve6bg1QwxsJWkgwVtlBUsOUHgS0sreNOEOvj75zDD8WSLm7CUv05WTHlKKSCylFodiRMjGkFGHo5uim8p0do90hu-6YXVey6w7ZdazsvLp3XvoJ7N-Nh7AKwI9AKiO_hfjP6f-6_gEwFqgQ</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Wang, Yitong</creator><creator>Xu, Bingfeng</creator><creator>Zhu, Lixia</creator><creator>Lou, Kun</creator><creator>Chen, Yingli</creator><creator>Zhao, Xia</creator><creator>Wang, Qian</creator><creator>Xu, Ling</creator><creator>Guo, Xiaohui</creator><creator>Ji, Linong</creator><creator>Cui, Yimin</creator><creator>Fang, Yi</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20171201</creationdate><title>Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus</title><author>Wang, Yitong ; Xu, Bingfeng ; Zhu, Lixia ; Lou, Kun ; Chen, Yingli ; Zhao, Xia ; Wang, Qian ; Xu, Ling ; Guo, Xiaohui ; Ji, Linong ; Cui, Yimin ; Fang, Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-a6400d95e203785f250801bdaffaaba68ce0c274ea34ecd9df40c19af3e84bd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Amino acids</topic><topic>Asian Continental Ancestry Group</topic><topic>Blood Glucose - drug effects</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Drug dosages</topic><topic>Fasting</topic><topic>Female</topic><topic>Glucagon-Like Peptide-1 Receptor - agonists</topic><topic>Glucose</topic><topic>Glycated Hemoglobin A - analysis</topic><topic>Half-Life</topic><topic>Hepatitis</topic><topic>Humans</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Injections, Subcutaneous</topic><topic>Insulin resistance</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine & Public Health</topic><topic>Metformin - administration & dosage</topic><topic>Middle Aged</topic><topic>Original Research Article</topic><topic>Peptides</topic><topic>Peptides - administration & dosage</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Postprandial Period - drug effects</topic><topic>Venoms - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yitong</creatorcontrib><creatorcontrib>Xu, Bingfeng</creatorcontrib><creatorcontrib>Zhu, Lixia</creatorcontrib><creatorcontrib>Lou, Kun</creatorcontrib><creatorcontrib>Chen, Yingli</creatorcontrib><creatorcontrib>Zhao, Xia</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Xu, Ling</creatorcontrib><creatorcontrib>Guo, Xiaohui</creatorcontrib><creatorcontrib>Ji, Linong</creatorcontrib><creatorcontrib>Cui, Yimin</creatorcontrib><creatorcontrib>Fang, Yi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Clinical drug investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yitong</au><au>Xu, Bingfeng</au><au>Zhu, Lixia</au><au>Lou, Kun</au><au>Chen, Yingli</au><au>Zhao, Xia</au><au>Wang, Qian</au><au>Xu, Ling</au><au>Guo, Xiaohui</au><au>Ji, Linong</au><au>Cui, Yimin</au><au>Fang, Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus</atitle><jtitle>Clinical drug investigation</jtitle><stitle>Clin Drug Investig</stitle><addtitle>Clin Drug Investig</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>37</volume><issue>12</issue><spage>1107</spage><epage>1115</epage><pages>1107-1115</pages><issn>1173-2563</issn><eissn>1179-1918</eissn><abstract>Background and Objectives
Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM).
Design and methods
In the randomized, open-label study, Chinese patients with T2DM (
n
= 36) were randomly assigned to three groups of rE-4 (
n
= 12), rE-4 with metformin (
n
= 12) and exenatide (
n
= 12, as the control group) for 12 weeks. rE-4 and exenatide were administered by subcutaneous injection in the abdomen, and metformin was given by oral administration. Patients received rE-4 or exenatide 5 μg twice a day for the first 4 weeks and adjusted the dose of rE-4 or exenatide to 10 μg twice a day at day 29 for the following 8 weeks, if their glycated albumin (GA) values were still greater than 17%. We evaluated pharmacokinetic parameters of rE-4 and exenatide, fasting plasma glucose (FPG), 2-h postprandial blood glucose (PG2 h), glycosylated hemoglobin (HbA1c) and body weight at designated time points.
Results
Thirty-six patients were enrolled, and 29 subjects finished the study. rE-4 was absorbed quickly with a median peak-reaching time (
t
max
) of 0.8–1.5 h and eliminated rapidly with a median terminal half-life (
t
1/2z
) of 1.6–1.9 h. The exposure of rE-4 increased in an approximately dose-proportional method without accumulation. rE-4 10 μg twice a day could reduce FPG (~2.29 mmol/L), PG2 h (~6.00 mmol/L), HbA1c (~1.19%) and body weight (~0.48 kg) from baseline to 12 weeks, with no statistical significance compared with exenatide (FPG: ~1.88 mmol/L; PG2 h: ~6.66 mmol/L; HbA1c: ~1.13%; body weight: ~0.47 kg) and rE-4 with metformin (FPG: ~2.33 mmol/L; PG2 h: ~6.51 mmol/L; HbA1c: ~0.84%; body weight: ~1.16 kg) (
p
> 0.05).
Conclusions
rE-4 twice a day has a pharmacokinetic profile similar to exenatide and rE-4 with metformin after single and multiple doses in Chinese patients with T2DM. Also, rE-4 could improve glycemic control effectively.
ClinicalTrials.gov identifier
NCT01342042.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>28932995</pmid><doi>10.1007/s40261-017-0569-1</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1173-2563 |
| ispartof | Clinical drug investigation, 2017-12, Vol.37 (12), p.1107-1115 |
| issn | 1173-2563 1179-1918 |
| language | eng |
| recordid | cdi_proquest_journals_1990423443 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adult Amino acids Asian Continental Ancestry Group Blood Glucose - drug effects Diabetes Diabetes Mellitus, Type 2 - drug therapy Drug dosages Fasting Female Glucagon-Like Peptide-1 Receptor - agonists Glucose Glycated Hemoglobin A - analysis Half-Life Hepatitis Humans Hypoglycemic Agents - administration & dosage Injections, Subcutaneous Insulin resistance Internal Medicine Male Medicine & Public Health Metformin - administration & dosage Middle Aged Original Research Article Peptides Peptides - administration & dosage Pharmaceutical sciences Pharmacodynamics Pharmacokinetics Pharmacology/Toxicology Pharmacotherapy Postprandial Period - drug effects Venoms - administration & dosage |
| title | Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T21%3A38%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pharmacokinetics%20and%20Preliminary%20Pharmacodynamics%20of%20Single-%20and%20Multiple-dose%20Lyophilized%20Recombinant%20Glucagon-like%20Peptide-1%20Receptor%20Agonist%20(rE-4)%20in%20Chinese%20Patients%20with%20Type%202%20Diabetes%20Mellitus&rft.jtitle=Clinical%20drug%20investigation&rft.au=Wang,%20Yitong&rft.date=2017-12-01&rft.volume=37&rft.issue=12&rft.spage=1107&rft.epage=1115&rft.pages=1107-1115&rft.issn=1173-2563&rft.eissn=1179-1918&rft_id=info:doi/10.1007/s40261-017-0569-1&rft_dat=%3Cproquest_cross%3E1990423443%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1990423443&rft_id=info:pmid/28932995&rfr_iscdi=true |