Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9‐39) for treatment of post‐bariatric hypoglycaemia
Aim To evaluate the safety, efficacy and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9‐39) in patients with post‐bariatric hypoglycaemia (PBH). Methods In this phase 2, multiple‐ascending‐dose study conducted at Stanford University, 19 women with PBH...
Gespeichert in:
| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2020-08, Vol.22 (8), p.1406-1416 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1416 |
|---|---|
| container_issue | 8 |
| container_start_page | 1406 |
| container_title | Diabetes, obesity & metabolism |
| container_volume | 22 |
| creator | Tan, Marilyn Lamendola, Cynthia Luong, Roger McLaughlin, Tracey Craig, Colleen |
| description | Aim
To evaluate the safety, efficacy and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9‐39) in patients with post‐bariatric hypoglycaemia (PBH).
Methods
In this phase 2, multiple‐ascending‐dose study conducted at Stanford University, 19 women with PBH underwent a baseline oral glucose tolerance test (OGTT), with metabolic and symptomatic assessments. Fourteen were then sequentially assigned to receive one of four ascending‐dose levels of twice‐daily lyophilized (Lyo) avexitide by SC injection for 3 days. On the basis of safety, efficacy and tolerability, five additional participants then received a novel liquid formulation (Liq) of avexitide by SC injection at a fixed dose of 30 mg twice daily for 3 days. All 19 participants underwent a repeat OGTT on day 3 of dosing to quantify metabolic, symptomatic and pharmacokinetic responses.
Results
Treatment with Lyo avexitide reduced the magnitude of symptomatic hyperinsulinaemic hypoglycaemia at all dose levels, with dose‐dependent improvements in glucose nadir, insulin peak and symptom score; doses ≥20 mg twice daily did not require glycaemic rescue (administered at glucose |
| doi_str_mv | 10.1111/dom.14048 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2420896662</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2420896662</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3538-6e72af433addc95bb702d61dc5e6ad6a9411b6a66dc990248d97bc7435bb09963</originalsourceid><addsrcrecordid>eNp1kMtu1TAQhi0EohdY8ALIEhsqkda3OPGyKuUiFXUBrKOJPWldTuJgO9DseAR4RZ4En57CDm_G0v_NP9JHyDPOjnl5Jy6Mx1wx1T4g-1xpWXEp9MO7v6haw8QeOUjphjGmZNs8JntSiJrVku2TXx9hwLy-ojgM3oJdKUyOztcQR7Dhi58we5toGGjEGSHTtPR2yTBhWBJ1IfnpapvCN7z12TukL_EWJ-cnan7_-CnNER1CpDmW3RGnvGXnkHLJeogecvSWXq9zuNqsFnD08IQ8GmCT8On9PCSf35x_OntXXVy-fX92elFZWcu20tgIGJSU4Jw1dd83TDjNna1Rg9NgFOe9Bq1LWgyo1pmmt42SBWXGaHlIXux65xi-LphydxOWOJWTnVCCtUZrLQp1tKNsDClFHLo5-hHi2nHWbeV3RX53J7-wz-8bl35E94_8a7sAJzvgu9_g-v-m7vXlh13lH3Pckgs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2420896662</pqid></control><display><type>article</type><title>Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9‐39) for treatment of post‐bariatric hypoglycaemia</title><source>Wiley Online Library All Journals</source><creator>Tan, Marilyn ; Lamendola, Cynthia ; Luong, Roger ; McLaughlin, Tracey ; Craig, Colleen</creator><creatorcontrib>Tan, Marilyn ; Lamendola, Cynthia ; Luong, Roger ; McLaughlin, Tracey ; Craig, Colleen</creatorcontrib><description>Aim
To evaluate the safety, efficacy and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9‐39) in patients with post‐bariatric hypoglycaemia (PBH).
Methods
In this phase 2, multiple‐ascending‐dose study conducted at Stanford University, 19 women with PBH underwent a baseline oral glucose tolerance test (OGTT), with metabolic and symptomatic assessments. Fourteen were then sequentially assigned to receive one of four ascending‐dose levels of twice‐daily lyophilized (Lyo) avexitide by SC injection for 3 days. On the basis of safety, efficacy and tolerability, five additional participants then received a novel liquid formulation (Liq) of avexitide by SC injection at a fixed dose of 30 mg twice daily for 3 days. All 19 participants underwent a repeat OGTT on day 3 of dosing to quantify metabolic, symptomatic and pharmacokinetic responses.
Results
Treatment with Lyo avexitide reduced the magnitude of symptomatic hyperinsulinaemic hypoglycaemia at all dose levels, with dose‐dependent improvements in glucose nadir, insulin peak and symptom score; doses ≥20 mg twice daily did not require glycaemic rescue (administered at glucose <2.8 mmol/L). Participants receiving Liq avexitide 30 mg twice daily did not require any glycaemic rescue, and on average achieved a 47% increase in glucose nadir, a 67% reduction in peak insulin, and a 47% reduction in overall symptom score. Equivalent doses of Liq versus Lyo avexitide yielded higher and more sustained plasma concentrations. Both formulations were well tolerated.
Conclusions
In patients with PBH, twice‐daily administration of SC avexitide effectively raised the glucose nadir and prevented severe hypoglycaemia requiring rescue intervention. Avexitide may represent a viable therapy for PBH.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.14048</identifier><identifier>PMID: 32250530</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>bariatric surgery ; Dosage ; Gastrointestinal surgery ; GLP‐1 ; Glucose ; Glucose tolerance ; hypoglycaemia ; Hypoglycemia ; Injection ; Insulin ; Metabolism ; Obesity ; Pharmacokinetics ; Postoperative period ; Safety</subject><ispartof>Diabetes, obesity & metabolism, 2020-08, Vol.22 (8), p.1406-1416</ispartof><rights>2020 John Wiley & Sons Ltd</rights><rights>2020 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3538-6e72af433addc95bb702d61dc5e6ad6a9411b6a66dc990248d97bc7435bb09963</citedby><cites>FETCH-LOGICAL-c3538-6e72af433addc95bb702d61dc5e6ad6a9411b6a66dc990248d97bc7435bb09963</cites><orcidid>0000-0003-1308-6440 ; 0000-0002-4829-8649 ; 0000-0002-6651-4691</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.14048$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.14048$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32250530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tan, Marilyn</creatorcontrib><creatorcontrib>Lamendola, Cynthia</creatorcontrib><creatorcontrib>Luong, Roger</creatorcontrib><creatorcontrib>McLaughlin, Tracey</creatorcontrib><creatorcontrib>Craig, Colleen</creatorcontrib><title>Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9‐39) for treatment of post‐bariatric hypoglycaemia</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
To evaluate the safety, efficacy and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9‐39) in patients with post‐bariatric hypoglycaemia (PBH).
Methods
In this phase 2, multiple‐ascending‐dose study conducted at Stanford University, 19 women with PBH underwent a baseline oral glucose tolerance test (OGTT), with metabolic and symptomatic assessments. Fourteen were then sequentially assigned to receive one of four ascending‐dose levels of twice‐daily lyophilized (Lyo) avexitide by SC injection for 3 days. On the basis of safety, efficacy and tolerability, five additional participants then received a novel liquid formulation (Liq) of avexitide by SC injection at a fixed dose of 30 mg twice daily for 3 days. All 19 participants underwent a repeat OGTT on day 3 of dosing to quantify metabolic, symptomatic and pharmacokinetic responses.
Results
Treatment with Lyo avexitide reduced the magnitude of symptomatic hyperinsulinaemic hypoglycaemia at all dose levels, with dose‐dependent improvements in glucose nadir, insulin peak and symptom score; doses ≥20 mg twice daily did not require glycaemic rescue (administered at glucose <2.8 mmol/L). Participants receiving Liq avexitide 30 mg twice daily did not require any glycaemic rescue, and on average achieved a 47% increase in glucose nadir, a 67% reduction in peak insulin, and a 47% reduction in overall symptom score. Equivalent doses of Liq versus Lyo avexitide yielded higher and more sustained plasma concentrations. Both formulations were well tolerated.
Conclusions
In patients with PBH, twice‐daily administration of SC avexitide effectively raised the glucose nadir and prevented severe hypoglycaemia requiring rescue intervention. Avexitide may represent a viable therapy for PBH.</description><subject>bariatric surgery</subject><subject>Dosage</subject><subject>Gastrointestinal surgery</subject><subject>GLP‐1</subject><subject>Glucose</subject><subject>Glucose tolerance</subject><subject>hypoglycaemia</subject><subject>Hypoglycemia</subject><subject>Injection</subject><subject>Insulin</subject><subject>Metabolism</subject><subject>Obesity</subject><subject>Pharmacokinetics</subject><subject>Postoperative period</subject><subject>Safety</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kMtu1TAQhi0EohdY8ALIEhsqkda3OPGyKuUiFXUBrKOJPWldTuJgO9DseAR4RZ4En57CDm_G0v_NP9JHyDPOjnl5Jy6Mx1wx1T4g-1xpWXEp9MO7v6haw8QeOUjphjGmZNs8JntSiJrVku2TXx9hwLy-ojgM3oJdKUyOztcQR7Dhi58we5toGGjEGSHTtPR2yTBhWBJ1IfnpapvCN7z12TukL_EWJ-cnan7_-CnNER1CpDmW3RGnvGXnkHLJeogecvSWXq9zuNqsFnD08IQ8GmCT8On9PCSf35x_OntXXVy-fX92elFZWcu20tgIGJSU4Jw1dd83TDjNna1Rg9NgFOe9Bq1LWgyo1pmmt42SBWXGaHlIXux65xi-LphydxOWOJWTnVCCtUZrLQp1tKNsDClFHLo5-hHi2nHWbeV3RX53J7-wz-8bl35E94_8a7sAJzvgu9_g-v-m7vXlh13lH3Pckgs</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Tan, Marilyn</creator><creator>Lamendola, Cynthia</creator><creator>Luong, Roger</creator><creator>McLaughlin, Tracey</creator><creator>Craig, Colleen</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><orcidid>https://orcid.org/0000-0003-1308-6440</orcidid><orcidid>https://orcid.org/0000-0002-4829-8649</orcidid><orcidid>https://orcid.org/0000-0002-6651-4691</orcidid></search><sort><creationdate>202008</creationdate><title>Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9‐39) for treatment of post‐bariatric hypoglycaemia</title><author>Tan, Marilyn ; Lamendola, Cynthia ; Luong, Roger ; McLaughlin, Tracey ; Craig, Colleen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-6e72af433addc95bb702d61dc5e6ad6a9411b6a66dc990248d97bc7435bb09963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>bariatric surgery</topic><topic>Dosage</topic><topic>Gastrointestinal surgery</topic><topic>GLP‐1</topic><topic>Glucose</topic><topic>Glucose tolerance</topic><topic>hypoglycaemia</topic><topic>Hypoglycemia</topic><topic>Injection</topic><topic>Insulin</topic><topic>Metabolism</topic><topic>Obesity</topic><topic>Pharmacokinetics</topic><topic>Postoperative period</topic><topic>Safety</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tan, Marilyn</creatorcontrib><creatorcontrib>Lamendola, Cynthia</creatorcontrib><creatorcontrib>Luong, Roger</creatorcontrib><creatorcontrib>McLaughlin, Tracey</creatorcontrib><creatorcontrib>Craig, Colleen</creatorcontrib><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><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Marilyn</au><au>Lamendola, Cynthia</au><au>Luong, Roger</au><au>McLaughlin, Tracey</au><au>Craig, Colleen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9‐39) for treatment of post‐bariatric hypoglycaemia</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2020-08</date><risdate>2020</risdate><volume>22</volume><issue>8</issue><spage>1406</spage><epage>1416</epage><pages>1406-1416</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aim
To evaluate the safety, efficacy and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9‐39) in patients with post‐bariatric hypoglycaemia (PBH).
Methods
In this phase 2, multiple‐ascending‐dose study conducted at Stanford University, 19 women with PBH underwent a baseline oral glucose tolerance test (OGTT), with metabolic and symptomatic assessments. Fourteen were then sequentially assigned to receive one of four ascending‐dose levels of twice‐daily lyophilized (Lyo) avexitide by SC injection for 3 days. On the basis of safety, efficacy and tolerability, five additional participants then received a novel liquid formulation (Liq) of avexitide by SC injection at a fixed dose of 30 mg twice daily for 3 days. All 19 participants underwent a repeat OGTT on day 3 of dosing to quantify metabolic, symptomatic and pharmacokinetic responses.
Results
Treatment with Lyo avexitide reduced the magnitude of symptomatic hyperinsulinaemic hypoglycaemia at all dose levels, with dose‐dependent improvements in glucose nadir, insulin peak and symptom score; doses ≥20 mg twice daily did not require glycaemic rescue (administered at glucose <2.8 mmol/L). Participants receiving Liq avexitide 30 mg twice daily did not require any glycaemic rescue, and on average achieved a 47% increase in glucose nadir, a 67% reduction in peak insulin, and a 47% reduction in overall symptom score. Equivalent doses of Liq versus Lyo avexitide yielded higher and more sustained plasma concentrations. Both formulations were well tolerated.
Conclusions
In patients with PBH, twice‐daily administration of SC avexitide effectively raised the glucose nadir and prevented severe hypoglycaemia requiring rescue intervention. Avexitide may represent a viable therapy for PBH.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>32250530</pmid><doi>10.1111/dom.14048</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1308-6440</orcidid><orcidid>https://orcid.org/0000-0002-4829-8649</orcidid><orcidid>https://orcid.org/0000-0002-6651-4691</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1462-8902 |
| ispartof | Diabetes, obesity & metabolism, 2020-08, Vol.22 (8), p.1406-1416 |
| issn | 1462-8902 1463-1326 |
| language | eng |
| recordid | cdi_proquest_journals_2420896662 |
| source | Wiley Online Library All Journals |
| subjects | bariatric surgery Dosage Gastrointestinal surgery GLP‐1 Glucose Glucose tolerance hypoglycaemia Hypoglycemia Injection Insulin Metabolism Obesity Pharmacokinetics Postoperative period Safety |
| title | Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9‐39) for treatment of post‐bariatric hypoglycaemia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T08%3A31%3A31IST&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=Safety,%20efficacy%20and%20pharmacokinetics%20of%20repeat%20subcutaneous%20dosing%20of%20avexitide%20(exendin%209%E2%80%9039)%20for%20treatment%20of%20post%E2%80%90bariatric%20hypoglycaemia&rft.jtitle=Diabetes,%20obesity%20&%20metabolism&rft.au=Tan,%20Marilyn&rft.date=2020-08&rft.volume=22&rft.issue=8&rft.spage=1406&rft.epage=1416&rft.pages=1406-1416&rft.issn=1462-8902&rft.eissn=1463-1326&rft_id=info:doi/10.1111/dom.14048&rft_dat=%3Cproquest_cross%3E2420896662%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=2420896662&rft_id=info:pmid/32250530&rfr_iscdi=true |