Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis
Abstract Context Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce. Objective We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM. Method PubMed, E...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2023-12, Vol.109 (1), p.279-292 |
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| creator | Park, Jeayoung Ntelis, Spyridon Yunasan, Elvina Downton, Katherine D Yip, Terry Cheuk-Fung Munir, Kashif M Haq, Nowreen |
| description | Abstract
Context
Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce.
Objective
We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM.
Method
PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool.
Results
A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (−0.09%/mg), weight (−2.2 kg/mg), and TDI (−4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (−0.51% vs −0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse.
Conclusion
Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits. |
| doi_str_mv | 10.1210/clinem/dgad471 |
| format | Article |
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Context
Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce.
Objective
We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM.
Method
PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool.
Results
A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (−0.09%/mg), weight (−2.2 kg/mg), and TDI (−4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (−0.51% vs −0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse.
Conclusion
Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgad471</identifier><identifier>PMID: 37561012</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Body weight ; Care and treatment ; Diabetes Mellitus, Type 1 - complications ; Diabetes Mellitus, Type 1 - drug therapy ; Diabetes Mellitus, Type 2 - complications ; Diabetes therapy ; Glucagon ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Glycated Hemoglobin ; Glycosylated hemoglobin ; Health aspects ; Humans ; Hypoglycemic agents ; Hypoglycemic Agents - therapeutic use ; Insulin - therapeutic use ; Liraglutide - therapeutic use ; Type 1 diabetes ; Type 2 diabetes ; Venoms ; Weight Loss</subject><ispartof>The journal of clinical endocrinology and metabolism, 2023-12, Vol.109 (1), p.279-292</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2024 Oxford University Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-2c2ef181443a28202623d5f55eb8927afdf86f6929940a05c863cb0db13895393</citedby><cites>FETCH-LOGICAL-c396t-2c2ef181443a28202623d5f55eb8927afdf86f6929940a05c863cb0db13895393</cites><orcidid>0000-0003-0659-2249 ; 0000-0002-1075-1284 ; 0000-0002-5812-1038 ; 0000-0002-1819-2464</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37561012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Jeayoung</creatorcontrib><creatorcontrib>Ntelis, Spyridon</creatorcontrib><creatorcontrib>Yunasan, Elvina</creatorcontrib><creatorcontrib>Downton, Katherine D</creatorcontrib><creatorcontrib>Yip, Terry Cheuk-Fung</creatorcontrib><creatorcontrib>Munir, Kashif M</creatorcontrib><creatorcontrib>Haq, Nowreen</creatorcontrib><title>Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Context
Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce.
Objective
We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM.
Method
PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool.
Results
A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (−0.09%/mg), weight (−2.2 kg/mg), and TDI (−4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (−0.51% vs −0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse.
Conclusion
Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.</description><subject>Body weight</subject><subject>Care and treatment</subject><subject>Diabetes Mellitus, Type 1 - complications</subject><subject>Diabetes Mellitus, Type 1 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes therapy</subject><subject>Glucagon</subject><subject>Glucagon-Like Peptide 1</subject><subject>Glucagon-Like Peptide-1 Receptor</subject><subject>Glycated Hemoglobin</subject><subject>Glycosylated hemoglobin</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hypoglycemic agents</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Insulin - therapeutic use</subject><subject>Liraglutide - therapeutic use</subject><subject>Type 1 diabetes</subject><subject>Type 2 diabetes</subject><subject>Venoms</subject><subject>Weight Loss</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rFEEQhhtRzBq9epQGL3qYpD_mo9vbEjUKKwbdoLehprt603G-nO6JzE_wX9vLrp4CUoeC4nnfquIl5DlnZ1xwdm5a32N3bndg84o_ICuu8yKruK4ekhVjgme6Et9PyJMQbhnjeV7Ix-REVkXJGRcr8vuynQ3shj7b-B9Ir3CM3iLldN1DO-xmDBQCXdvbuTfR3yHd3uAE40LdMNEriB77GOg3H2_odhn3wrceGowY3iQLej1aiGjp1yVE7BJu6Be88_iLQm_pJ4yQQVq0BB-ekkcO2oDPjv2UXL9_t734kG0-X368WG8yI3UZM2EEOq7SJxKEEkyUQtrCFQU2SosKnHWqdKUWWucMWGFUKU3DbMOl0oXU8pS8OviO0_Az_RfrzgeDbQs9DnOohcqVynkpVUJfHtAdtFj73g1xArPH63VV6YJxzliizu6hUlnsvBl6dD7N7xOYaQhhQlePk-9gWmrO6n2q9SHV-phqErw4njw3Hdp_-N8YE_D6AAzz-D-zPy9GrAg</recordid><startdate>20231221</startdate><enddate>20231221</enddate><creator>Park, Jeayoung</creator><creator>Ntelis, Spyridon</creator><creator>Yunasan, Elvina</creator><creator>Downton, Katherine D</creator><creator>Yip, Terry Cheuk-Fung</creator><creator>Munir, Kashif M</creator><creator>Haq, Nowreen</creator><general>Oxford University Press</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>7X8</scope><orcidid>https://orcid.org/0000-0003-0659-2249</orcidid><orcidid>https://orcid.org/0000-0002-1075-1284</orcidid><orcidid>https://orcid.org/0000-0002-5812-1038</orcidid><orcidid>https://orcid.org/0000-0002-1819-2464</orcidid></search><sort><creationdate>20231221</creationdate><title>Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis</title><author>Park, Jeayoung ; Ntelis, Spyridon ; Yunasan, Elvina ; Downton, Katherine D ; Yip, Terry Cheuk-Fung ; Munir, Kashif M ; Haq, Nowreen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-2c2ef181443a28202623d5f55eb8927afdf86f6929940a05c863cb0db13895393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Body weight</topic><topic>Care and treatment</topic><topic>Diabetes Mellitus, Type 1 - complications</topic><topic>Diabetes Mellitus, Type 1 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes therapy</topic><topic>Glucagon</topic><topic>Glucagon-Like Peptide 1</topic><topic>Glucagon-Like Peptide-1 Receptor</topic><topic>Glycated Hemoglobin</topic><topic>Glycosylated hemoglobin</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hypoglycemic agents</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Insulin - therapeutic use</topic><topic>Liraglutide - therapeutic use</topic><topic>Type 1 diabetes</topic><topic>Type 2 diabetes</topic><topic>Venoms</topic><topic>Weight Loss</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Jeayoung</creatorcontrib><creatorcontrib>Ntelis, Spyridon</creatorcontrib><creatorcontrib>Yunasan, Elvina</creatorcontrib><creatorcontrib>Downton, Katherine D</creatorcontrib><creatorcontrib>Yip, Terry Cheuk-Fung</creatorcontrib><creatorcontrib>Munir, Kashif M</creatorcontrib><creatorcontrib>Haq, Nowreen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Jeayoung</au><au>Ntelis, Spyridon</au><au>Yunasan, Elvina</au><au>Downton, Katherine D</au><au>Yip, Terry Cheuk-Fung</au><au>Munir, Kashif M</au><au>Haq, Nowreen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2023-12-21</date><risdate>2023</risdate><volume>109</volume><issue>1</issue><spage>279</spage><epage>292</epage><pages>279-292</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Abstract
Context
Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce.
Objective
We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM.
Method
PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool.
Results
A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (−0.09%/mg), weight (−2.2 kg/mg), and TDI (−4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (−0.51% vs −0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse.
Conclusion
Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>37561012</pmid><doi>10.1210/clinem/dgad471</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-0659-2249</orcidid><orcidid>https://orcid.org/0000-0002-1075-1284</orcidid><orcidid>https://orcid.org/0000-0002-5812-1038</orcidid><orcidid>https://orcid.org/0000-0002-1819-2464</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2023-12, Vol.109 (1), p.279-292 |
| issn | 0021-972X 1945-7197 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Body weight Care and treatment Diabetes Mellitus, Type 1 - complications Diabetes Mellitus, Type 1 - drug therapy Diabetes Mellitus, Type 2 - complications Diabetes therapy Glucagon Glucagon-Like Peptide 1 Glucagon-Like Peptide-1 Receptor Glycated Hemoglobin Glycosylated hemoglobin Health aspects Humans Hypoglycemic agents Hypoglycemic Agents - therapeutic use Insulin - therapeutic use Liraglutide - therapeutic use Type 1 diabetes Type 2 diabetes Venoms Weight Loss |
| title | Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis |
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