Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
Aim To assess the efficacy and safety of recently approved once‐weekly glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes. Methods We conducted a systematic review and meta‐analysis of randomized controlled trials comparing any GLP‐1 RA licensed for once‐weekly do...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2015-11, Vol.17 (11), p.1065-1074 |
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| creator | Karagiannis, T. Liakos, A. Bekiari, E. Athanasiadou, E. Paschos, P. Vasilakou, D. Mainou, M. Rika, M. Boura, P. Matthews, D. R. Tsapas, A. |
| description | Aim
To assess the efficacy and safety of recently approved once‐weekly glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes.
Methods
We conducted a systematic review and meta‐analysis of randomized controlled trials comparing any GLP‐1 RA licensed for once‐weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate.
Results
In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was −0.66% [six studies; 95% confidence interval (CI) −1.14 to −0.19; I2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I2 = 65%) with dulaglutide. Based on data from placebo‐controlled trials, we did not detect statistically significant weight‐sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once‐weekly GLP‐1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c‐lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I2 = 40% and −0.28; 95% CI −0.45 to −0.10; I2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions.
Conclusions
Given their dosing scheme and overall efficacy and safety profile, once‐weekly GLP‐1 RAs are a convenient therapeutic option for use as add‐on to metformin. |
| doi_str_mv | 10.1111/dom.12541 |
| format | Article |
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To assess the efficacy and safety of recently approved once‐weekly glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes.
Methods
We conducted a systematic review and meta‐analysis of randomized controlled trials comparing any GLP‐1 RA licensed for once‐weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate.
Results
In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was −0.66% [six studies; 95% confidence interval (CI) −1.14 to −0.19; I2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I2 = 65%) with dulaglutide. Based on data from placebo‐controlled trials, we did not detect statistically significant weight‐sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once‐weekly GLP‐1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c‐lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I2 = 40% and −0.28; 95% CI −0.45 to −0.10; I2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions.
Conclusions
Given their dosing scheme and overall efficacy and safety profile, once‐weekly GLP‐1 RAs are a convenient therapeutic option for use as add‐on to metformin.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.12541</identifier><identifier>PMID: 26395850</identifier><identifier>CODEN: DOMEF6</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject><![CDATA[Adult ; Agonists ; Antidiabetics ; Clinical trials ; Confidence intervals ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - drug therapy ; Dosage ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; GLP-1 ; GLP-1 analogue ; GLP-1 receptor agonists ; Glucagon ; Glucagon-Like Peptide 1 - administration & dosage ; Glucagon-Like Peptide 1 - agonists ; Glucagon-Like Peptide 1 - analogs & derivatives ; Glucagon-Like Peptides - administration & dosage ; Glucagon-Like Peptides - analogs & derivatives ; Glycated Hemoglobin A - drug effects ; Hemoglobin ; Humans ; Hypoglycemic Agents - administration & dosage ; Immunoglobulin Fc Fragments - administration & dosage ; incretin therapy ; Incretins - administration & dosage ; Male ; Meta-analysis ; Metformin ; Metformin - administration & dosage ; Peptides ; Peptides - administration & dosage ; Placebos ; Randomized Controlled Trials as Topic ; Recombinant Fusion Proteins - administration & dosage ; Safety ; Statistical analysis ; Systematic review ; type 2 diabetes ; Venoms - administration & dosage]]></subject><ispartof>Diabetes, obesity & metabolism, 2015-11, Vol.17 (11), p.1065-1074</ispartof><rights>2015 John Wiley & Sons Ltd</rights><rights>2015 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4191-3409c74d80a941aaf026a4d87608fb95443bf9111cac2ad18f3342830c463adb3</citedby><cites>FETCH-LOGICAL-c4191-3409c74d80a941aaf026a4d87608fb95443bf9111cac2ad18f3342830c463adb3</cites><orcidid>0000-0003-0221-4072 ; 0000-0003-3261-2979</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.12541$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.12541$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26395850$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karagiannis, T.</creatorcontrib><creatorcontrib>Liakos, A.</creatorcontrib><creatorcontrib>Bekiari, E.</creatorcontrib><creatorcontrib>Athanasiadou, E.</creatorcontrib><creatorcontrib>Paschos, P.</creatorcontrib><creatorcontrib>Vasilakou, D.</creatorcontrib><creatorcontrib>Mainou, M.</creatorcontrib><creatorcontrib>Rika, M.</creatorcontrib><creatorcontrib>Boura, P.</creatorcontrib><creatorcontrib>Matthews, D. R.</creatorcontrib><creatorcontrib>Tsapas, A.</creatorcontrib><title>Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
To assess the efficacy and safety of recently approved once‐weekly glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes.
Methods
We conducted a systematic review and meta‐analysis of randomized controlled trials comparing any GLP‐1 RA licensed for once‐weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate.
Results
In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was −0.66% [six studies; 95% confidence interval (CI) −1.14 to −0.19; I2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I2 = 65%) with dulaglutide. Based on data from placebo‐controlled trials, we did not detect statistically significant weight‐sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once‐weekly GLP‐1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c‐lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I2 = 40% and −0.28; 95% CI −0.45 to −0.10; I2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions.
Conclusions
Given their dosing scheme and overall efficacy and safety profile, once‐weekly GLP‐1 RAs are a convenient therapeutic option for use as add‐on to metformin.</description><subject>Adult</subject><subject>Agonists</subject><subject>Antidiabetics</subject><subject>Clinical trials</subject><subject>Confidence intervals</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Dosage</subject><subject>Drug Administration Schedule</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>GLP-1</subject><subject>GLP-1 analogue</subject><subject>GLP-1 receptor agonists</subject><subject>Glucagon</subject><subject>Glucagon-Like Peptide 1 - administration & dosage</subject><subject>Glucagon-Like Peptide 1 - agonists</subject><subject>Glucagon-Like Peptide 1 - analogs & derivatives</subject><subject>Glucagon-Like Peptides - administration & dosage</subject><subject>Glucagon-Like Peptides - analogs & derivatives</subject><subject>Glycated Hemoglobin A - drug effects</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Immunoglobulin Fc Fragments - administration & dosage</subject><subject>incretin therapy</subject><subject>Incretins - administration & dosage</subject><subject>Male</subject><subject>Meta-analysis</subject><subject>Metformin</subject><subject>Metformin - administration & dosage</subject><subject>Peptides</subject><subject>Peptides - administration & dosage</subject><subject>Placebos</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Recombinant Fusion Proteins - administration & dosage</subject><subject>Safety</subject><subject>Statistical analysis</subject><subject>Systematic review</subject><subject>type 2 diabetes</subject><subject>Venoms - administration & dosage</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhSMEoqWw4AWQJTawSOu__LErpRSk0m4KdGd5nOvBnSQOtsMQ3oy3485M2wUSeON77e8cy-dm2XNGDxmuo9b3h4wXkj3I9pksRc4ELx9ua57XDeV72ZMYbyilUtTV42yPl6Ip6oLuZ79PrXVGm5nooSVRW0gz8Zb4wUC-Blh1M1l2k9FLP-SdWwEZYUyuBcJIAIO1D2Rz6WKKxGKTvgHp9aCX0MOQNl5pHoFw0jq9gATxDdEkzjFBr5Mz6PLDwXr7fA9J5yjt5ujiRhnw1PfuF7TE-CEF33VYpuB0F59mjyxu8Ox2P8g-vz-9OvmQn1-efTw5Ps-NZA3LhaSNqWRbU91IprWlvNTYViWt7aIppBQL22CKGALXLautEJLXghoMUrcLcZC92vmOwX-fICbVu2ig6_QAfoqKVbwoMHAmEX35F3rjp4D_iUrQopFUyrL4H4VekgteVCVSr3eUCT7GAFaNwfU6zIpRtZm6wmTUdurIvrh1nBY9tPfk3ZgRONoBa9fB_G8n9e7y051lvlPgXOHnvUKHlSorURXq68WZ-nJ9JZq311xdiD9Nb8bU</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>Karagiannis, T.</creator><creator>Liakos, A.</creator><creator>Bekiari, E.</creator><creator>Athanasiadou, E.</creator><creator>Paschos, P.</creator><creator>Vasilakou, D.</creator><creator>Mainou, M.</creator><creator>Rika, M.</creator><creator>Boura, P.</creator><creator>Matthews, D. R.</creator><creator>Tsapas, A.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0221-4072</orcidid><orcidid>https://orcid.org/0000-0003-3261-2979</orcidid></search><sort><creationdate>201511</creationdate><title>Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials</title><author>Karagiannis, T. ; Liakos, A. ; Bekiari, E. ; Athanasiadou, E. ; Paschos, P. ; Vasilakou, D. ; Mainou, M. ; Rika, M. ; Boura, P. ; Matthews, D. R. ; Tsapas, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4191-3409c74d80a941aaf026a4d87608fb95443bf9111cac2ad18f3342830c463adb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Agonists</topic><topic>Antidiabetics</topic><topic>Clinical trials</topic><topic>Confidence intervals</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Dosage</topic><topic>Drug Administration Schedule</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>GLP-1</topic><topic>GLP-1 analogue</topic><topic>GLP-1 receptor agonists</topic><topic>Glucagon</topic><topic>Glucagon-Like Peptide 1 - administration & dosage</topic><topic>Glucagon-Like Peptide 1 - agonists</topic><topic>Glucagon-Like Peptide 1 - analogs & derivatives</topic><topic>Glucagon-Like Peptides - administration & dosage</topic><topic>Glucagon-Like Peptides - analogs & derivatives</topic><topic>Glycated Hemoglobin A - drug effects</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Immunoglobulin Fc Fragments - administration & dosage</topic><topic>incretin therapy</topic><topic>Incretins - administration & dosage</topic><topic>Male</topic><topic>Meta-analysis</topic><topic>Metformin</topic><topic>Metformin - administration & dosage</topic><topic>Peptides</topic><topic>Peptides - administration & dosage</topic><topic>Placebos</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Recombinant Fusion Proteins - administration & dosage</topic><topic>Safety</topic><topic>Statistical analysis</topic><topic>Systematic review</topic><topic>type 2 diabetes</topic><topic>Venoms - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karagiannis, T.</creatorcontrib><creatorcontrib>Liakos, A.</creatorcontrib><creatorcontrib>Bekiari, E.</creatorcontrib><creatorcontrib>Athanasiadou, E.</creatorcontrib><creatorcontrib>Paschos, P.</creatorcontrib><creatorcontrib>Vasilakou, D.</creatorcontrib><creatorcontrib>Mainou, M.</creatorcontrib><creatorcontrib>Rika, M.</creatorcontrib><creatorcontrib>Boura, P.</creatorcontrib><creatorcontrib>Matthews, D. R.</creatorcontrib><creatorcontrib>Tsapas, A.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</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>Karagiannis, T.</au><au>Liakos, A.</au><au>Bekiari, E.</au><au>Athanasiadou, E.</au><au>Paschos, P.</au><au>Vasilakou, D.</au><au>Mainou, M.</au><au>Rika, M.</au><au>Boura, P.</au><au>Matthews, D. R.</au><au>Tsapas, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2015-11</date><risdate>2015</risdate><volume>17</volume><issue>11</issue><spage>1065</spage><epage>1074</epage><pages>1065-1074</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><coden>DOMEF6</coden><abstract>Aim
To assess the efficacy and safety of recently approved once‐weekly glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes.
Methods
We conducted a systematic review and meta‐analysis of randomized controlled trials comparing any GLP‐1 RA licensed for once‐weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate.
Results
In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was −0.66% [six studies; 95% confidence interval (CI) −1.14 to −0.19; I2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I2 = 65%) with dulaglutide. Based on data from placebo‐controlled trials, we did not detect statistically significant weight‐sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once‐weekly GLP‐1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c‐lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I2 = 40% and −0.28; 95% CI −0.45 to −0.10; I2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions.
Conclusions
Given their dosing scheme and overall efficacy and safety profile, once‐weekly GLP‐1 RAs are a convenient therapeutic option for use as add‐on to metformin.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>26395850</pmid><doi>10.1111/dom.12541</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0221-4072</orcidid><orcidid>https://orcid.org/0000-0003-3261-2979</orcidid></addata></record> |
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| ispartof | Diabetes, obesity & metabolism, 2015-11, Vol.17 (11), p.1065-1074 |
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| language | eng |
| recordid | cdi_proquest_miscellaneous_1725513214 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Agonists Antidiabetics Clinical trials Confidence intervals Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - drug therapy Dosage Drug Administration Schedule Drug Therapy, Combination Female GLP-1 GLP-1 analogue GLP-1 receptor agonists Glucagon Glucagon-Like Peptide 1 - administration & dosage Glucagon-Like Peptide 1 - agonists Glucagon-Like Peptide 1 - analogs & derivatives Glucagon-Like Peptides - administration & dosage Glucagon-Like Peptides - analogs & derivatives Glycated Hemoglobin A - drug effects Hemoglobin Humans Hypoglycemic Agents - administration & dosage Immunoglobulin Fc Fragments - administration & dosage incretin therapy Incretins - administration & dosage Male Meta-analysis Metformin Metformin - administration & dosage Peptides Peptides - administration & dosage Placebos Randomized Controlled Trials as Topic Recombinant Fusion Proteins - administration & dosage Safety Statistical analysis Systematic review type 2 diabetes Venoms - administration & dosage |
| title | Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials |
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