Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes
Aims To investigate the pharmacokinetic/pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes (T1D). Materials and Methods In this randomized, open‐label, two‐period crossover trial, 66 individuals with T1D (age 18–64 years; glycated haemoglobin ≤75 mmol/mol [≤...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2024-05, Vol.26 (5), p.1941-1949 |
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| container_issue | 5 |
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| container_title | Diabetes, obesity & metabolism |
| container_volume | 26 |
| creator | Hövelmann, Ulrike Engberg, Susanne Heise, Tim Kristensen, Niels Rode Nørgreen, Lea Zijlstra, Eric Ribel‐Madsen, Rasmus |
| description | Aims
To investigate the pharmacokinetic/pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes (T1D).
Materials and Methods
In this randomized, open‐label, two‐period crossover trial, 66 individuals with T1D (age 18–64 years; glycated haemoglobin ≤75 mmol/mol [≤ 9%]) were to receive once‐weekly icodec (8 weeks) and once‐daily insulin glargine U100 (2 weeks) at individualized fixed equimolar total weekly doses established during up to 10 weeks' run‐in with glargine U100 titrated to pre‐breakfast plasma glucose (PG) of 4.4–7.2 mmol/L (80–130 mg/dL). Insulin aspart was used as bolus insulin. Blood sampling for icodec pharmacokinetics was performed from the first icodec dose until 35 days after the last dose. The glucose infusion rate at steady state was assessed in glucose clamps (target 6.7 mmol/L [120 mg/dL]) at 16–52 h and 138–168 h after the last icodec dose and 0–24 h after the last glargine U100 dose. Icodec pharmacodynamics during 1 week were predicted by pharmacokinetic‐pharmacodynamic modelling. Hypoglycaemia was recorded during the treatment periods based on self‐measured PG.
Results
Icodec reached pharmacokinetic steady state on average within 2–3 weeks. At steady state, model‐predicted daily proportions of glucose infusion rate during the 1‐week dosing interval were 14.3%, 19.6%, 18.3%, 15.7%, 13.1%, 10.6% and 8.4%, respectively. Rates and duration of Level 2 hypoglycaemic episodes (PG |
| doi_str_mv | 10.1111/dom.15510 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2929538468</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2929538468</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3480-bcd199598e1fb193c101ca3f81026845391af3b331211db3d9c085f134e449ae3</originalsourceid><addsrcrecordid>eNp1kc1u1TAQhS0EoqWw4AWQJTawSOvJOPfaS1R-paKygLXl2BPVbeIEO-lVdjwCz8iT4PZeWCAxmxnNfDo6msPYcxCnUOrMj8MpNA2IB-wY5AYrwHrz8H6uK6VFfcSe5HwthJCoto_ZESrcaiHqY5a-XNk0WDfehEhzcNxGz6fDzq_RDmU3pXGiNAfKfOz4GB39-vFzR3TTrzzEvPQh8lBwcvxuij7cBr_YPvNdmK_4vE7EgftgW5opP2WPunKjZ4d-wr69f_f1_GN1cfnh0_mbi8qhVKJqnQetG60IuhY0OhDgLHYKRL1RskENtsMWEWoA36LXTqimA5QkpbaEJ-zVXrfY_75Qns0QsqO-t5HGJZta17pBJTeqoC__Qa_HJcXizqBAWd7ZbHWhXu8pl8acE3VmSmGwaTUgzF0QpgRh7oMo7IuD4tIO5P-Sfz5fgLM9sAs9rf9XMm8vP-8lfwNYN5Ms</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3034132579</pqid></control><display><type>article</type><title>Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Hövelmann, Ulrike ; Engberg, Susanne ; Heise, Tim ; Kristensen, Niels Rode ; Nørgreen, Lea ; Zijlstra, Eric ; Ribel‐Madsen, Rasmus</creator><creatorcontrib>Hövelmann, Ulrike ; Engberg, Susanne ; Heise, Tim ; Kristensen, Niels Rode ; Nørgreen, Lea ; Zijlstra, Eric ; Ribel‐Madsen, Rasmus</creatorcontrib><description>Aims
To investigate the pharmacokinetic/pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes (T1D).
Materials and Methods
In this randomized, open‐label, two‐period crossover trial, 66 individuals with T1D (age 18–64 years; glycated haemoglobin ≤75 mmol/mol [≤ 9%]) were to receive once‐weekly icodec (8 weeks) and once‐daily insulin glargine U100 (2 weeks) at individualized fixed equimolar total weekly doses established during up to 10 weeks' run‐in with glargine U100 titrated to pre‐breakfast plasma glucose (PG) of 4.4–7.2 mmol/L (80–130 mg/dL). Insulin aspart was used as bolus insulin. Blood sampling for icodec pharmacokinetics was performed from the first icodec dose until 35 days after the last dose. The glucose infusion rate at steady state was assessed in glucose clamps (target 6.7 mmol/L [120 mg/dL]) at 16–52 h and 138–168 h after the last icodec dose and 0–24 h after the last glargine U100 dose. Icodec pharmacodynamics during 1 week were predicted by pharmacokinetic‐pharmacodynamic modelling. Hypoglycaemia was recorded during the treatment periods based on self‐measured PG.
Results
Icodec reached pharmacokinetic steady state on average within 2–3 weeks. At steady state, model‐predicted daily proportions of glucose infusion rate during the 1‐week dosing interval were 14.3%, 19.6%, 18.3%, 15.7%, 13.1%, 10.6% and 8.4%, respectively. Rates and duration of Level 2 hypoglycaemic episodes (PG <3.0 mmol/L [54 mg/dL]) were 32.8 versus 23.9 episodes per participant‐year of exposure and 33 ± 25 versus 30 ± 18 min (mean ± SD) for icodec versus glargine U100.
Conclusions
The pharmacokinetic/pharmacodynamic properties of icodec suggest its potential to provide basal coverage in a basal‐bolus insulin regimen in people with T1D.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.15510</identifier><identifier>PMID: 38379002</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>basal insulin ; Diabetes ; Diabetes mellitus (insulin dependent) ; Dosage ; Glucose ; Hemoglobin ; Hypoglycemia ; Insulin ; insulin analogues ; Pharmacodynamics ; Pharmacokinetics ; phase I–II study ; type 1 diabetes</subject><ispartof>Diabetes, obesity & metabolism, 2024-05, Vol.26 (5), p.1941-1949</ispartof><rights>2024 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3480-bcd199598e1fb193c101ca3f81026845391af3b331211db3d9c085f134e449ae3</cites><orcidid>0000-0001-8843-5452 ; 0000-0002-8346-2037 ; 0000-0002-0940-8972</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.15510$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.15510$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,777,781,1413,27906,27907,45556,45557</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38379002$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hövelmann, Ulrike</creatorcontrib><creatorcontrib>Engberg, Susanne</creatorcontrib><creatorcontrib>Heise, Tim</creatorcontrib><creatorcontrib>Kristensen, Niels Rode</creatorcontrib><creatorcontrib>Nørgreen, Lea</creatorcontrib><creatorcontrib>Zijlstra, Eric</creatorcontrib><creatorcontrib>Ribel‐Madsen, Rasmus</creatorcontrib><title>Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aims
To investigate the pharmacokinetic/pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes (T1D).
Materials and Methods
In this randomized, open‐label, two‐period crossover trial, 66 individuals with T1D (age 18–64 years; glycated haemoglobin ≤75 mmol/mol [≤ 9%]) were to receive once‐weekly icodec (8 weeks) and once‐daily insulin glargine U100 (2 weeks) at individualized fixed equimolar total weekly doses established during up to 10 weeks' run‐in with glargine U100 titrated to pre‐breakfast plasma glucose (PG) of 4.4–7.2 mmol/L (80–130 mg/dL). Insulin aspart was used as bolus insulin. Blood sampling for icodec pharmacokinetics was performed from the first icodec dose until 35 days after the last dose. The glucose infusion rate at steady state was assessed in glucose clamps (target 6.7 mmol/L [120 mg/dL]) at 16–52 h and 138–168 h after the last icodec dose and 0–24 h after the last glargine U100 dose. Icodec pharmacodynamics during 1 week were predicted by pharmacokinetic‐pharmacodynamic modelling. Hypoglycaemia was recorded during the treatment periods based on self‐measured PG.
Results
Icodec reached pharmacokinetic steady state on average within 2–3 weeks. At steady state, model‐predicted daily proportions of glucose infusion rate during the 1‐week dosing interval were 14.3%, 19.6%, 18.3%, 15.7%, 13.1%, 10.6% and 8.4%, respectively. Rates and duration of Level 2 hypoglycaemic episodes (PG <3.0 mmol/L [54 mg/dL]) were 32.8 versus 23.9 episodes per participant‐year of exposure and 33 ± 25 versus 30 ± 18 min (mean ± SD) for icodec versus glargine U100.
Conclusions
The pharmacokinetic/pharmacodynamic properties of icodec suggest its potential to provide basal coverage in a basal‐bolus insulin regimen in people with T1D.</description><subject>basal insulin</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Dosage</subject><subject>Glucose</subject><subject>Hemoglobin</subject><subject>Hypoglycemia</subject><subject>Insulin</subject><subject>insulin analogues</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>phase I–II study</subject><subject>type 1 diabetes</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp1kc1u1TAQhS0EoqWw4AWQJTawSOvJOPfaS1R-paKygLXl2BPVbeIEO-lVdjwCz8iT4PZeWCAxmxnNfDo6msPYcxCnUOrMj8MpNA2IB-wY5AYrwHrz8H6uK6VFfcSe5HwthJCoto_ZESrcaiHqY5a-XNk0WDfehEhzcNxGz6fDzq_RDmU3pXGiNAfKfOz4GB39-vFzR3TTrzzEvPQh8lBwcvxuij7cBr_YPvNdmK_4vE7EgftgW5opP2WPunKjZ4d-wr69f_f1_GN1cfnh0_mbi8qhVKJqnQetG60IuhY0OhDgLHYKRL1RskENtsMWEWoA36LXTqimA5QkpbaEJ-zVXrfY_75Qns0QsqO-t5HGJZta17pBJTeqoC__Qa_HJcXizqBAWd7ZbHWhXu8pl8acE3VmSmGwaTUgzF0QpgRh7oMo7IuD4tIO5P-Sfz5fgLM9sAs9rf9XMm8vP-8lfwNYN5Ms</recordid><startdate>202405</startdate><enddate>202405</enddate><creator>Hövelmann, Ulrike</creator><creator>Engberg, Susanne</creator><creator>Heise, Tim</creator><creator>Kristensen, Niels Rode</creator><creator>Nørgreen, Lea</creator><creator>Zijlstra, Eric</creator><creator>Ribel‐Madsen, Rasmus</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8843-5452</orcidid><orcidid>https://orcid.org/0000-0002-8346-2037</orcidid><orcidid>https://orcid.org/0000-0002-0940-8972</orcidid></search><sort><creationdate>202405</creationdate><title>Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes</title><author>Hövelmann, Ulrike ; Engberg, Susanne ; Heise, Tim ; Kristensen, Niels Rode ; Nørgreen, Lea ; Zijlstra, Eric ; Ribel‐Madsen, Rasmus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3480-bcd199598e1fb193c101ca3f81026845391af3b331211db3d9c085f134e449ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>basal insulin</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Dosage</topic><topic>Glucose</topic><topic>Hemoglobin</topic><topic>Hypoglycemia</topic><topic>Insulin</topic><topic>insulin analogues</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>phase I–II study</topic><topic>type 1 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hövelmann, Ulrike</creatorcontrib><creatorcontrib>Engberg, Susanne</creatorcontrib><creatorcontrib>Heise, Tim</creatorcontrib><creatorcontrib>Kristensen, Niels Rode</creatorcontrib><creatorcontrib>Nørgreen, Lea</creatorcontrib><creatorcontrib>Zijlstra, Eric</creatorcontrib><creatorcontrib>Ribel‐Madsen, Rasmus</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hövelmann, Ulrike</au><au>Engberg, Susanne</au><au>Heise, Tim</au><au>Kristensen, Niels Rode</au><au>Nørgreen, Lea</au><au>Zijlstra, Eric</au><au>Ribel‐Madsen, Rasmus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2024-05</date><risdate>2024</risdate><volume>26</volume><issue>5</issue><spage>1941</spage><epage>1949</epage><pages>1941-1949</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aims
To investigate the pharmacokinetic/pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes (T1D).
Materials and Methods
In this randomized, open‐label, two‐period crossover trial, 66 individuals with T1D (age 18–64 years; glycated haemoglobin ≤75 mmol/mol [≤ 9%]) were to receive once‐weekly icodec (8 weeks) and once‐daily insulin glargine U100 (2 weeks) at individualized fixed equimolar total weekly doses established during up to 10 weeks' run‐in with glargine U100 titrated to pre‐breakfast plasma glucose (PG) of 4.4–7.2 mmol/L (80–130 mg/dL). Insulin aspart was used as bolus insulin. Blood sampling for icodec pharmacokinetics was performed from the first icodec dose until 35 days after the last dose. The glucose infusion rate at steady state was assessed in glucose clamps (target 6.7 mmol/L [120 mg/dL]) at 16–52 h and 138–168 h after the last icodec dose and 0–24 h after the last glargine U100 dose. Icodec pharmacodynamics during 1 week were predicted by pharmacokinetic‐pharmacodynamic modelling. Hypoglycaemia was recorded during the treatment periods based on self‐measured PG.
Results
Icodec reached pharmacokinetic steady state on average within 2–3 weeks. At steady state, model‐predicted daily proportions of glucose infusion rate during the 1‐week dosing interval were 14.3%, 19.6%, 18.3%, 15.7%, 13.1%, 10.6% and 8.4%, respectively. Rates and duration of Level 2 hypoglycaemic episodes (PG <3.0 mmol/L [54 mg/dL]) were 32.8 versus 23.9 episodes per participant‐year of exposure and 33 ± 25 versus 30 ± 18 min (mean ± SD) for icodec versus glargine U100.
Conclusions
The pharmacokinetic/pharmacodynamic properties of icodec suggest its potential to provide basal coverage in a basal‐bolus insulin regimen in people with T1D.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>38379002</pmid><doi>10.1111/dom.15510</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8843-5452</orcidid><orcidid>https://orcid.org/0000-0002-8346-2037</orcidid><orcidid>https://orcid.org/0000-0002-0940-8972</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | basal insulin Diabetes Diabetes mellitus (insulin dependent) Dosage Glucose Hemoglobin Hypoglycemia Insulin insulin analogues Pharmacodynamics Pharmacokinetics phase I–II study type 1 diabetes |
| title | Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 1 diabetes |
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