Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function
Aims/Introduction The present multicenter, prospective, controlled, open and randomized three‐arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function. Materials and Methods Type 2 diabetes patients treated with 750 mg of metformin (hemogl...
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| Veröffentlicht in: | Journal of diabetes investigation 2017-05, Vol.8 (3), p.330-340 |
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| container_title | Journal of diabetes investigation |
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| creator | Shigiyama, Fumika Kumashiro, Naoki Miyagi, Masahiko Iga, Ryo Kobayashi, Yuka Kanda, Eiichiro Uchino, Hiroshi Hirose, Takahisa |
| description | Aims/Introduction
The present multicenter, prospective, controlled, open and randomized three‐arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.
Materials and Methods
Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and |
| doi_str_mv | 10.1111/jdi.12587 |
| format | Article |
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The present multicenter, prospective, controlled, open and randomized three‐arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.
Materials and Methods
Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add‐on group, n = 29) and treated for 16 weeks. Vascular endothelial function was evaluated by flow‐mediated dilation. The primary end‐point was changes in flow‐mediated dilation at 16 weeks relative to baseline.
Results
Linagliptin significantly improved flow‐mediated dilation from baseline (4.9 ± 2.7%) to 16 weeks (6.3 ± 2.7%, P < 0.05), whereas the other groups did not show any changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and linagliptin add‐on groups compared with the control (6.6 ± 0.6%, 6.5 ± 0.5% and 7.0 ± 0.6%, respectively). Single and multiple regression analyses showed that apolipoprotein B correlated significantly with change in flow‐mediated dilation, and apolipoprotein B was decreased only in the linagliptin add‐on group (–6.0 ± 11.3 mg/dL, P < 0.01).
Conclusions
Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.
Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.</description><identifier>ISSN: 2040-1116</identifier><identifier>EISSN: 2040-1124</identifier><identifier>DOI: 10.1111/jdi.12587</identifier><identifier>PMID: 27868359</identifier><language>eng</language><publisher>Japan: John Wiley & Sons, Inc</publisher><subject>Aged ; Apolipoprotein B ; Apolipoproteins ; Cardiovascular Diseases - complications ; Cardiovascular Diseases - drug therapy ; Clinical Trial ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - complications ; Endothelial function ; Female ; Hemoglobin ; Humans ; Hyperglycemia ; Hypoglycemic Agents - therapeutic use ; Linagliptin ; Linagliptin - therapeutic use ; Low density lipoprotein ; Male ; Metformin ; Metformin - therapeutic use ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Type 2 diabetes</subject><ispartof>Journal of diabetes investigation, 2017-05, Vol.8 (3), p.330-340</ispartof><rights>2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd</rights><rights>2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by-nc-nd/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><citedby>FETCH-LOGICAL-c5797-e1d216c70df3ba611a44d3838f5b0236ac551df06b08ea992ee5d8f979574f5f3</citedby><cites>FETCH-LOGICAL-c5797-e1d216c70df3ba611a44d3838f5b0236ac551df06b08ea992ee5d8f979574f5f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415473/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415473/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27868359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shigiyama, Fumika</creatorcontrib><creatorcontrib>Kumashiro, Naoki</creatorcontrib><creatorcontrib>Miyagi, Masahiko</creatorcontrib><creatorcontrib>Iga, Ryo</creatorcontrib><creatorcontrib>Kobayashi, Yuka</creatorcontrib><creatorcontrib>Kanda, Eiichiro</creatorcontrib><creatorcontrib>Uchino, Hiroshi</creatorcontrib><creatorcontrib>Hirose, Takahisa</creatorcontrib><title>Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function</title><title>Journal of diabetes investigation</title><addtitle>J Diabetes Investig</addtitle><description>Aims/Introduction
The present multicenter, prospective, controlled, open and randomized three‐arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.
Materials and Methods
Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add‐on group, n = 29) and treated for 16 weeks. Vascular endothelial function was evaluated by flow‐mediated dilation. The primary end‐point was changes in flow‐mediated dilation at 16 weeks relative to baseline.
Results
Linagliptin significantly improved flow‐mediated dilation from baseline (4.9 ± 2.7%) to 16 weeks (6.3 ± 2.7%, P < 0.05), whereas the other groups did not show any changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and linagliptin add‐on groups compared with the control (6.6 ± 0.6%, 6.5 ± 0.5% and 7.0 ± 0.6%, respectively). Single and multiple regression analyses showed that apolipoprotein B correlated significantly with change in flow‐mediated dilation, and apolipoprotein B was decreased only in the linagliptin add‐on group (–6.0 ± 11.3 mg/dL, P < 0.01).
Conclusions
Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.
Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.</description><subject>Aged</subject><subject>Apolipoprotein B</subject><subject>Apolipoproteins</subject><subject>Cardiovascular Diseases - complications</subject><subject>Cardiovascular Diseases - drug therapy</subject><subject>Clinical Trial</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Endothelial function</subject><subject>Female</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Linagliptin</subject><subject>Linagliptin - therapeutic use</subject><subject>Low density lipoprotein</subject><subject>Male</subject><subject>Metformin</subject><subject>Metformin - therapeutic use</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Treatment Outcome</subject><subject>Type 2 diabetes</subject><issn>2040-1116</issn><issn>2040-1124</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUFvFCEUx4nR2Kb24BcwJF70sC0wA8N4MGlaa2s28aJnwgyPLpsZGIHZZv0a_cJSt91Uo1wgeT9-7738EXpNyQkt53Rt3AllXDbP0CEjNVlQyurn-zcVB-g4pTUpp5JSiOYlOmCNFLLi7SG6WzqvbwY3ZeexG6cYNpAweBPyCganB2xn32cXStXjSWcHPid86_IK5-0EmGHjdAcZ0gd8hqMuP0f3EwxOeTZbHCwennQAa6HYNuAhJVyk_-r0Cr2wekhw_HAfoe-Xn76dXy2WXz9fn58tFz1v2mYB1DAq-oYYW3VaUKrr2lSykpZ3hFVC95xTY4noiATdtgyAG2nbpuVNbbmtjtDHnXeauxFMXzaLelBTdKOOWxW0U39WvFupm7BRvKa8bqoiePcgiOHHDCmr0aUehkF7CHNSVNaMcyFEXdC3f6HrMEdf1itUy4kQjLeFer-j-hhSimD3w1Ci7tNWJW31O-3Cvnk6_Z58zLYApzvg1g2w_b9Jfbm43il_Ad9kt68</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Shigiyama, Fumika</creator><creator>Kumashiro, Naoki</creator><creator>Miyagi, Masahiko</creator><creator>Iga, Ryo</creator><creator>Kobayashi, Yuka</creator><creator>Kanda, Eiichiro</creator><creator>Uchino, Hiroshi</creator><creator>Hirose, Takahisa</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>3V.</scope><scope>7T5</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201705</creationdate><title>Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function</title><author>Shigiyama, Fumika ; Kumashiro, Naoki ; Miyagi, Masahiko ; Iga, Ryo ; Kobayashi, Yuka ; Kanda, Eiichiro ; Uchino, Hiroshi ; Hirose, Takahisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5797-e1d216c70df3ba611a44d3838f5b0236ac551df06b08ea992ee5d8f979574f5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Apolipoprotein B</topic><topic>Apolipoproteins</topic><topic>Cardiovascular Diseases - complications</topic><topic>Cardiovascular Diseases - drug therapy</topic><topic>Clinical Trial</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Endothelial function</topic><topic>Female</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Linagliptin</topic><topic>Linagliptin - therapeutic use</topic><topic>Low density lipoprotein</topic><topic>Male</topic><topic>Metformin</topic><topic>Metformin - therapeutic use</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Treatment Outcome</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shigiyama, Fumika</creatorcontrib><creatorcontrib>Kumashiro, Naoki</creatorcontrib><creatorcontrib>Miyagi, Masahiko</creatorcontrib><creatorcontrib>Iga, Ryo</creatorcontrib><creatorcontrib>Kobayashi, Yuka</creatorcontrib><creatorcontrib>Kanda, Eiichiro</creatorcontrib><creatorcontrib>Uchino, Hiroshi</creatorcontrib><creatorcontrib>Hirose, Takahisa</creatorcontrib><collection>Wiley Online Library Open Access</collection><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>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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 Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of diabetes investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shigiyama, Fumika</au><au>Kumashiro, Naoki</au><au>Miyagi, Masahiko</au><au>Iga, Ryo</au><au>Kobayashi, Yuka</au><au>Kanda, Eiichiro</au><au>Uchino, Hiroshi</au><au>Hirose, Takahisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function</atitle><jtitle>Journal of diabetes investigation</jtitle><addtitle>J Diabetes Investig</addtitle><date>2017-05</date><risdate>2017</risdate><volume>8</volume><issue>3</issue><spage>330</spage><epage>340</epage><pages>330-340</pages><issn>2040-1116</issn><eissn>2040-1124</eissn><abstract>Aims/Introduction
The present multicenter, prospective, controlled, open and randomized three‐arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.
Materials and Methods
Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add‐on group, n = 29) and treated for 16 weeks. Vascular endothelial function was evaluated by flow‐mediated dilation. The primary end‐point was changes in flow‐mediated dilation at 16 weeks relative to baseline.
Results
Linagliptin significantly improved flow‐mediated dilation from baseline (4.9 ± 2.7%) to 16 weeks (6.3 ± 2.7%, P < 0.05), whereas the other groups did not show any changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and linagliptin add‐on groups compared with the control (6.6 ± 0.6%, 6.5 ± 0.5% and 7.0 ± 0.6%, respectively). Single and multiple regression analyses showed that apolipoprotein B correlated significantly with change in flow‐mediated dilation, and apolipoprotein B was decreased only in the linagliptin add‐on group (–6.0 ± 11.3 mg/dL, P < 0.01).
Conclusions
Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.
Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.</abstract><cop>Japan</cop><pub>John Wiley & Sons, Inc</pub><pmid>27868359</pmid><doi>10.1111/jdi.12587</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Apolipoprotein B Apolipoproteins Cardiovascular Diseases - complications Cardiovascular Diseases - drug therapy Clinical Trial Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - complications Endothelial function Female Hemoglobin Humans Hyperglycemia Hypoglycemic Agents - therapeutic use Linagliptin Linagliptin - therapeutic use Low density lipoprotein Male Metformin Metformin - therapeutic use Middle Aged Prospective Studies Treatment Outcome Type 2 diabetes |
| title | Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function |
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