Alirocumab vs usual lipid‐lowering care as add‐on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM‐DYSLIPIDEMIA randomized trial
Aim To compare alirocumab, a proprotein convertase subtilisin‐kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM‐DYSLIPIDEMIA trial (NCT02642159). Materials and Methods...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2018-06, Vol.20 (6), p.1479-1489 |
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| creator | Ray, Kausik K. Leiter, Lawrence A. Müller‐Wieland, Dirk Cariou, Bertrand Colhoun, Helen M. Henry, Robert R. Tinahones, Francisco J. Bujas‐Bobanovic, Maja Domenger, Catherine Letierce, Alexia Samuel, Rita Del Prato, Stefano |
| description | Aim
To compare alirocumab, a proprotein convertase subtilisin‐kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM‐DYSLIPIDEMIA trial (NCT02642159).
Materials and Methods
The UC options (no additional lipid‐lowering therapy; fenofibrate; ezetimibe; omega‐3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open‐label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non‐HDL cholesterol concentration was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. The primary efficacy endpoint was percentage change in non‐HDL cholesterol from baseline to week 24.
Results
The randomized population comprised 413 individuals (intention‐to‐treat population, n = 409; safety population, n = 412). At week 24, the mean non‐HDL cholesterol reductions were superior with alirocumab (−32.5% difference vs UC, 97.5% confidence interval −38.1 to −27.0; P |
| doi_str_mv | 10.1111/dom.13257 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5969299</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2036904210</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4437-684f080aa597b995a0f0830bd988e3e87f8b5ee02edb3dd4b021e277d9940403</originalsourceid><addsrcrecordid>eNp1Uc1uEzEQXiEqWgoHXgCNxKmHbb2298cckKIm0EiJgtRcerK860njane92LsJ4cQj8C68EU-Ck5QKDvjib8bfz1gTRW8ScpmEc6Vtc5kwmubPorOEZywORfb8gGlcCEJPo5fePxBCOCvyF9EpFZxleZqdRT9HtXG2GhpVwsbD4AdVQ206o399_1HbLTrT3kOlHILyoPS-bVvoLfhe9SagNTrV7SBA02qzMTo4eNiafg39rkOgoI0qsccgbzU05itq0Dt_CFHYGPUelmuExfju9nZyB-N5iAh4Nv08HU_m0xG4oLON-RZ0vTOqfhWdrEIGvn68z6Plx8ny-iaeLT5Nr0ezuOKc5XFW8BUpiFKpyEshUkVCyUipRVEgwyJfFWWKSCjqkmnNS0ITpHmuheCEE3YefTjadkPZoK6w7Z2qZedMo9xOWmXkvy-tWct7u5GpyAQVIhi8ezRw9suAvpcPdnBtGFlSwjJBOE32MRdHVuWs9w5XTwkJkfv1yvB5eVhv4L79e6Qn5p99BsLVkbA1Ne7-7yTHi_nR8jcx2rQy</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2036904210</pqid></control><display><type>article</type><title>Alirocumab vs usual lipid‐lowering care as add‐on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM‐DYSLIPIDEMIA randomized trial</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Ray, Kausik K. ; Leiter, Lawrence A. ; Müller‐Wieland, Dirk ; Cariou, Bertrand ; Colhoun, Helen M. ; Henry, Robert R. ; Tinahones, Francisco J. ; Bujas‐Bobanovic, Maja ; Domenger, Catherine ; Letierce, Alexia ; Samuel, Rita ; Del Prato, Stefano</creator><creatorcontrib>Ray, Kausik K. ; Leiter, Lawrence A. ; Müller‐Wieland, Dirk ; Cariou, Bertrand ; Colhoun, Helen M. ; Henry, Robert R. ; Tinahones, Francisco J. ; Bujas‐Bobanovic, Maja ; Domenger, Catherine ; Letierce, Alexia ; Samuel, Rita ; Del Prato, Stefano</creatorcontrib><description>Aim
To compare alirocumab, a proprotein convertase subtilisin‐kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM‐DYSLIPIDEMIA trial (NCT02642159).
Materials and Methods
The UC options (no additional lipid‐lowering therapy; fenofibrate; ezetimibe; omega‐3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open‐label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non‐HDL cholesterol concentration was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. The primary efficacy endpoint was percentage change in non‐HDL cholesterol from baseline to week 24.
Results
The randomized population comprised 413 individuals (intention‐to‐treat population, n = 409; safety population, n = 412). At week 24, the mean non‐HDL cholesterol reductions were superior with alirocumab (−32.5% difference vs UC, 97.5% confidence interval −38.1 to −27.0; P < .0001). Overall, 63.6% of alirocumab‐treated individuals were maintained on 75 mg every 2 weeks. Alirocumab also reduced LDL cholesterol (−43.0%), apolipoprotein B (−32.3%), total cholesterol (−24.6%) and LDL particle number (−37.8%) at week 24 vs UC (all P < .0001). Consistent with the overall trial comparison, alirocumab reduced non‐HDL cholesterol to a greater degree within each UC stratum at week 24. The incidence of treatment‐emergent adverse events was 68.4% (alirocumab) and 66.4% (UC). No clinically meaningful effect on glycated haemoglobin, or change in number of glucose‐lowering agents, was seen.
Conclusions
In individuals with T2DM and mixed dyslipidaemia on maximally tolerated statin, alirocumab showed superiority to UC in non‐HDL cholesterol reduction and was generally well tolerated.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.13257</identifier><identifier>PMID: 29436756</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal, Humanized ; Anticholesteremic Agents - administration & dosage ; Anticholesteremic Agents - adverse effects ; Apolipoprotein B ; Blood Glucose - metabolism ; Cholesterol ; Cholesterol, HDL - metabolism ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - drug therapy ; Double-Blind Method ; Drug Administration Schedule ; Drug Therapy, Combination ; Dyslipidemia ; Dyslipidemias - drug therapy ; Evidence-based medicine ; Female ; Fenofibrate ; Glycated Hemoglobin - metabolism ; Hemoglobin ; High density lipoprotein ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - adverse effects ; Kexin ; Lipid Metabolism - drug effects ; Low density lipoprotein ; Male ; Metabolic disorders ; Middle Aged ; mixed dyslipidaemia ; Monoclonal antibodies ; Motivation ; Nicotinic acid ; non‐HDL cholesterol ; Omega-3 fatty acids ; Original ; PCSK9 ; Proprotein Convertase 9 - metabolism ; Proprotein convertases ; Statins ; Subtilisin ; Treatment Outcome ; type 2 diabetes</subject><ispartof>Diabetes, obesity & metabolism, 2018-06, Vol.20 (6), p.1479-1489</ispartof><rights>2018 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.</rights><rights>2018. This article 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-c4437-684f080aa597b995a0f0830bd988e3e87f8b5ee02edb3dd4b021e277d9940403</citedby><cites>FETCH-LOGICAL-c4437-684f080aa597b995a0f0830bd988e3e87f8b5ee02edb3dd4b021e277d9940403</cites><orcidid>0000-0002-7166-060X ; 0000-0002-4821-0117 ; 0000-0002-5388-0270 ; 0000-0002-1040-6229</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.13257$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.13257$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29436756$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ray, Kausik K.</creatorcontrib><creatorcontrib>Leiter, Lawrence A.</creatorcontrib><creatorcontrib>Müller‐Wieland, Dirk</creatorcontrib><creatorcontrib>Cariou, Bertrand</creatorcontrib><creatorcontrib>Colhoun, Helen M.</creatorcontrib><creatorcontrib>Henry, Robert R.</creatorcontrib><creatorcontrib>Tinahones, Francisco J.</creatorcontrib><creatorcontrib>Bujas‐Bobanovic, Maja</creatorcontrib><creatorcontrib>Domenger, Catherine</creatorcontrib><creatorcontrib>Letierce, Alexia</creatorcontrib><creatorcontrib>Samuel, Rita</creatorcontrib><creatorcontrib>Del Prato, Stefano</creatorcontrib><title>Alirocumab vs usual lipid‐lowering care as add‐on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM‐DYSLIPIDEMIA randomized trial</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
To compare alirocumab, a proprotein convertase subtilisin‐kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM‐DYSLIPIDEMIA trial (NCT02642159).
Materials and Methods
The UC options (no additional lipid‐lowering therapy; fenofibrate; ezetimibe; omega‐3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open‐label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non‐HDL cholesterol concentration was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. The primary efficacy endpoint was percentage change in non‐HDL cholesterol from baseline to week 24.
Results
The randomized population comprised 413 individuals (intention‐to‐treat population, n = 409; safety population, n = 412). At week 24, the mean non‐HDL cholesterol reductions were superior with alirocumab (−32.5% difference vs UC, 97.5% confidence interval −38.1 to −27.0; P < .0001). Overall, 63.6% of alirocumab‐treated individuals were maintained on 75 mg every 2 weeks. Alirocumab also reduced LDL cholesterol (−43.0%), apolipoprotein B (−32.3%), total cholesterol (−24.6%) and LDL particle number (−37.8%) at week 24 vs UC (all P < .0001). Consistent with the overall trial comparison, alirocumab reduced non‐HDL cholesterol to a greater degree within each UC stratum at week 24. The incidence of treatment‐emergent adverse events was 68.4% (alirocumab) and 66.4% (UC). No clinically meaningful effect on glycated haemoglobin, or change in number of glucose‐lowering agents, was seen.
Conclusions
In individuals with T2DM and mixed dyslipidaemia on maximally tolerated statin, alirocumab showed superiority to UC in non‐HDL cholesterol reduction and was generally well tolerated.</description><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Anticholesteremic Agents - administration & dosage</subject><subject>Anticholesteremic Agents - adverse effects</subject><subject>Apolipoprotein B</subject><subject>Blood Glucose - metabolism</subject><subject>Cholesterol</subject><subject>Cholesterol, HDL - metabolism</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Drug Therapy, Combination</subject><subject>Dyslipidemia</subject><subject>Dyslipidemias - drug therapy</subject><subject>Evidence-based medicine</subject><subject>Female</subject><subject>Fenofibrate</subject><subject>Glycated Hemoglobin - metabolism</subject><subject>Hemoglobin</subject><subject>High density lipoprotein</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - adverse effects</subject><subject>Kexin</subject><subject>Lipid Metabolism - drug effects</subject><subject>Low density lipoprotein</subject><subject>Male</subject><subject>Metabolic disorders</subject><subject>Middle Aged</subject><subject>mixed dyslipidaemia</subject><subject>Monoclonal antibodies</subject><subject>Motivation</subject><subject>Nicotinic acid</subject><subject>non‐HDL cholesterol</subject><subject>Omega-3 fatty acids</subject><subject>Original</subject><subject>PCSK9</subject><subject>Proprotein Convertase 9 - metabolism</subject><subject>Proprotein convertases</subject><subject>Statins</subject><subject>Subtilisin</subject><subject>Treatment Outcome</subject><subject>type 2 diabetes</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1Uc1uEzEQXiEqWgoHXgCNxKmHbb2298cckKIm0EiJgtRcerK860njane92LsJ4cQj8C68EU-Ck5QKDvjib8bfz1gTRW8ScpmEc6Vtc5kwmubPorOEZywORfb8gGlcCEJPo5fePxBCOCvyF9EpFZxleZqdRT9HtXG2GhpVwsbD4AdVQ206o399_1HbLTrT3kOlHILyoPS-bVvoLfhe9SagNTrV7SBA02qzMTo4eNiafg39rkOgoI0qsccgbzU05itq0Dt_CFHYGPUelmuExfju9nZyB-N5iAh4Nv08HU_m0xG4oLON-RZ0vTOqfhWdrEIGvn68z6Plx8ny-iaeLT5Nr0ezuOKc5XFW8BUpiFKpyEshUkVCyUipRVEgwyJfFWWKSCjqkmnNS0ITpHmuheCEE3YefTjadkPZoK6w7Z2qZedMo9xOWmXkvy-tWct7u5GpyAQVIhi8ezRw9suAvpcPdnBtGFlSwjJBOE32MRdHVuWs9w5XTwkJkfv1yvB5eVhv4L79e6Qn5p99BsLVkbA1Ne7-7yTHi_nR8jcx2rQy</recordid><startdate>201806</startdate><enddate>201806</enddate><creator>Ray, Kausik K.</creator><creator>Leiter, Lawrence A.</creator><creator>Müller‐Wieland, Dirk</creator><creator>Cariou, Bertrand</creator><creator>Colhoun, Helen M.</creator><creator>Henry, Robert R.</creator><creator>Tinahones, Francisco J.</creator><creator>Bujas‐Bobanovic, Maja</creator><creator>Domenger, Catherine</creator><creator>Letierce, Alexia</creator><creator>Samuel, Rita</creator><creator>Del Prato, Stefano</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, 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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7166-060X</orcidid><orcidid>https://orcid.org/0000-0002-4821-0117</orcidid><orcidid>https://orcid.org/0000-0002-5388-0270</orcidid><orcidid>https://orcid.org/0000-0002-1040-6229</orcidid></search><sort><creationdate>201806</creationdate><title>Alirocumab vs usual lipid‐lowering care as add‐on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM‐DYSLIPIDEMIA randomized trial</title><author>Ray, Kausik K. ; Leiter, Lawrence A. ; Müller‐Wieland, Dirk ; Cariou, Bertrand ; Colhoun, Helen M. ; Henry, Robert R. ; Tinahones, Francisco J. ; Bujas‐Bobanovic, Maja ; Domenger, Catherine ; Letierce, Alexia ; Samuel, Rita ; Del Prato, Stefano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4437-684f080aa597b995a0f0830bd988e3e87f8b5ee02edb3dd4b021e277d9940403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Anticholesteremic Agents - administration & dosage</topic><topic>Anticholesteremic Agents - adverse effects</topic><topic>Apolipoprotein B</topic><topic>Blood Glucose - metabolism</topic><topic>Cholesterol</topic><topic>Cholesterol, HDL - metabolism</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Drug Therapy, Combination</topic><topic>Dyslipidemia</topic><topic>Dyslipidemias - drug therapy</topic><topic>Evidence-based medicine</topic><topic>Female</topic><topic>Fenofibrate</topic><topic>Glycated Hemoglobin - metabolism</topic><topic>Hemoglobin</topic><topic>High density lipoprotein</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - adverse effects</topic><topic>Kexin</topic><topic>Lipid Metabolism - drug effects</topic><topic>Low density lipoprotein</topic><topic>Male</topic><topic>Metabolic disorders</topic><topic>Middle Aged</topic><topic>mixed dyslipidaemia</topic><topic>Monoclonal antibodies</topic><topic>Motivation</topic><topic>Nicotinic acid</topic><topic>non‐HDL cholesterol</topic><topic>Omega-3 fatty acids</topic><topic>Original</topic><topic>PCSK9</topic><topic>Proprotein Convertase 9 - metabolism</topic><topic>Proprotein convertases</topic><topic>Statins</topic><topic>Subtilisin</topic><topic>Treatment Outcome</topic><topic>type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ray, Kausik K.</creatorcontrib><creatorcontrib>Leiter, Lawrence A.</creatorcontrib><creatorcontrib>Müller‐Wieland, Dirk</creatorcontrib><creatorcontrib>Cariou, Bertrand</creatorcontrib><creatorcontrib>Colhoun, Helen M.</creatorcontrib><creatorcontrib>Henry, Robert R.</creatorcontrib><creatorcontrib>Tinahones, Francisco J.</creatorcontrib><creatorcontrib>Bujas‐Bobanovic, Maja</creatorcontrib><creatorcontrib>Domenger, Catherine</creatorcontrib><creatorcontrib>Letierce, Alexia</creatorcontrib><creatorcontrib>Samuel, Rita</creatorcontrib><creatorcontrib>Del Prato, Stefano</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>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ray, Kausik K.</au><au>Leiter, Lawrence A.</au><au>Müller‐Wieland, Dirk</au><au>Cariou, Bertrand</au><au>Colhoun, Helen M.</au><au>Henry, Robert R.</au><au>Tinahones, Francisco J.</au><au>Bujas‐Bobanovic, Maja</au><au>Domenger, Catherine</au><au>Letierce, Alexia</au><au>Samuel, Rita</au><au>Del Prato, Stefano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alirocumab vs usual lipid‐lowering care as add‐on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM‐DYSLIPIDEMIA randomized trial</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2018-06</date><risdate>2018</risdate><volume>20</volume><issue>6</issue><spage>1479</spage><epage>1489</epage><pages>1479-1489</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aim
To compare alirocumab, a proprotein convertase subtilisin‐kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM‐DYSLIPIDEMIA trial (NCT02642159).
Materials and Methods
The UC options (no additional lipid‐lowering therapy; fenofibrate; ezetimibe; omega‐3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open‐label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non‐HDL cholesterol concentration was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. The primary efficacy endpoint was percentage change in non‐HDL cholesterol from baseline to week 24.
Results
The randomized population comprised 413 individuals (intention‐to‐treat population, n = 409; safety population, n = 412). At week 24, the mean non‐HDL cholesterol reductions were superior with alirocumab (−32.5% difference vs UC, 97.5% confidence interval −38.1 to −27.0; P < .0001). Overall, 63.6% of alirocumab‐treated individuals were maintained on 75 mg every 2 weeks. Alirocumab also reduced LDL cholesterol (−43.0%), apolipoprotein B (−32.3%), total cholesterol (−24.6%) and LDL particle number (−37.8%) at week 24 vs UC (all P < .0001). Consistent with the overall trial comparison, alirocumab reduced non‐HDL cholesterol to a greater degree within each UC stratum at week 24. The incidence of treatment‐emergent adverse events was 68.4% (alirocumab) and 66.4% (UC). No clinically meaningful effect on glycated haemoglobin, or change in number of glucose‐lowering agents, was seen.
Conclusions
In individuals with T2DM and mixed dyslipidaemia on maximally tolerated statin, alirocumab showed superiority to UC in non‐HDL cholesterol reduction and was generally well tolerated.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>29436756</pmid><doi>10.1111/dom.13257</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7166-060X</orcidid><orcidid>https://orcid.org/0000-0002-4821-0117</orcidid><orcidid>https://orcid.org/0000-0002-5388-0270</orcidid><orcidid>https://orcid.org/0000-0002-1040-6229</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1462-8902 |
| ispartof | Diabetes, obesity & metabolism, 2018-06, Vol.20 (6), p.1479-1489 |
| issn | 1462-8902 1463-1326 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5969299 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal, Humanized Anticholesteremic Agents - administration & dosage Anticholesteremic Agents - adverse effects Apolipoprotein B Blood Glucose - metabolism Cholesterol Cholesterol, HDL - metabolism Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - drug therapy Double-Blind Method Drug Administration Schedule Drug Therapy, Combination Dyslipidemia Dyslipidemias - drug therapy Evidence-based medicine Female Fenofibrate Glycated Hemoglobin - metabolism Hemoglobin High density lipoprotein Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - adverse effects Kexin Lipid Metabolism - drug effects Low density lipoprotein Male Metabolic disorders Middle Aged mixed dyslipidaemia Monoclonal antibodies Motivation Nicotinic acid non‐HDL cholesterol Omega-3 fatty acids Original PCSK9 Proprotein Convertase 9 - metabolism Proprotein convertases Statins Subtilisin Treatment Outcome type 2 diabetes |
| title | Alirocumab vs usual lipid‐lowering care as add‐on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM‐DYSLIPIDEMIA randomized trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T16%3A07%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alirocumab%20vs%20usual%20lipid%E2%80%90lowering%20care%20as%20add%E2%80%90on%20to%20statin%20therapy%20in%20individuals%20with%20type%202%20diabetes%20and%20mixed%20dyslipidaemia:%20The%20ODYSSEY%20DM%E2%80%90DYSLIPIDEMIA%20randomized%20trial&rft.jtitle=Diabetes,%20obesity%20&%20metabolism&rft.au=Ray,%20Kausik%20K.&rft.date=2018-06&rft.volume=20&rft.issue=6&rft.spage=1479&rft.epage=1489&rft.pages=1479-1489&rft.issn=1462-8902&rft.eissn=1463-1326&rft_id=info:doi/10.1111/dom.13257&rft_dat=%3Cproquest_pubme%3E2036904210%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2036904210&rft_id=info:pmid/29436756&rfr_iscdi=true |