Effects of the dual peroxisome proliferator–activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes
Background Insulin-resistant states, including type 2 diabetes (T2D) and prediabetes, are associated with elevated cardiovascular (CV) risk. Aleglitazar is a dual peroxisome proliferator–activated receptor α/γ agonist with favorable insulin-sensitizing and glucose-lowering actions, favorable effects...
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| Veröffentlicht in: | The American heart journal 2015-07, Vol.170 (1), p.117-122 |
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| creator | Erdmann, Erland, MD Califf, Robert, MD Gerstein, Hertzel C., MD Malmberg, Klas, MD Ruilope, Luis, MD Schwartz, Gregory G., MD Wedel, Hans, MD Volz, Dietmar, MD Ditmarsch, Marc, MD Svensson, Anders, MD Bengus, Monica, MD |
| description | Background Insulin-resistant states, including type 2 diabetes (T2D) and prediabetes, are associated with elevated cardiovascular (CV) risk. Aleglitazar is a dual peroxisome proliferator–activated receptor α/γ agonist with favorable insulin-sensitizing and glucose-lowering actions, favorable effects on blood lipids, and an acceptable safety profile in short-time studies. Therefore, it was hypothesized that aleglitazar would reduce CV morbidity and mortality in patients with T2D mellitus and prediabetes (defined as glycosylated hemoglobin ≥5.7% to |
| doi_str_mv | 10.1016/j.ahj.2015.03.021 |
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| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_512649</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0002870315001969</els_id><sourcerecordid>3717209381</sourcerecordid><originalsourceid>FETCH-LOGICAL-c544t-131ad3c47f91262dc4c309e9cf5653df1416147a512ad6cb3cbf778a50203f133</originalsourceid><addsrcrecordid>eNp9ks1uEzEQxy0EoiHwAFyQJS5cNvhrvWshIVWlfEiVOFDOluMdE6eb7GJ7W8KJN-DAG_IkTJRQpB44eTz6zX888zchTzlbcMb1y_XCrdYLwXi9YHLBBL9HZpyZptKNUvfJjDEmqrZh8oQ8ynmNVy1a_ZCcCM2MbBsxIz_PQwBfMh0CLSug3eR6OkIavsU8bICOaehjgOTKkH7_-OV8ideuQEcTeBgxSY-pfdTDlz4W990lGrd0dCXCFqVvYlnRy90IVNA30S2hQKYb6JGdsHHCJtAd84_Jg-D6DE-O55x8fnt-efa-uvj47sPZ6UXla6VKxSV3nfSqCYYLLTqvvGQGjA-1rmUXuOKaq8bVXLhO-6X0y9A0rauZYDJwKeekOujmGxinpR1T3Li0s4OL9pi6wggsKmhlkH9x4HEhXyfIxW5i9jiD28IwZcu1YVq1ArvPyfM76HqY0hanQao1sjZKaqT4gfJpyDlBuH0CZ3bvrl1bdNfu3bVMWnQXa54dlaflBrrbir92IvDqAACu7jpCstmjBx7Xi34V2w3xv_Kv71T7Pm6jd_0V7CD_m8JmYZn9tP9e-9_Fa8a40Ub-ATd7zS8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1689359436</pqid></control><display><type>article</type><title>Effects of the dual peroxisome proliferator–activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Erdmann, Erland, MD ; Califf, Robert, MD ; Gerstein, Hertzel C., MD ; Malmberg, Klas, MD ; Ruilope, Luis, MD ; Schwartz, Gregory G., MD ; Wedel, Hans, MD ; Volz, Dietmar, MD ; Ditmarsch, Marc, MD ; Svensson, Anders, MD ; Bengus, Monica, MD</creator><creatorcontrib>Erdmann, Erland, MD ; Califf, Robert, MD ; Gerstein, Hertzel C., MD ; Malmberg, Klas, MD ; Ruilope, Luis, MD ; Schwartz, Gregory G., MD ; Wedel, Hans, MD ; Volz, Dietmar, MD ; Ditmarsch, Marc, MD ; Svensson, Anders, MD ; Bengus, Monica, MD</creatorcontrib><description>Background Insulin-resistant states, including type 2 diabetes (T2D) and prediabetes, are associated with elevated cardiovascular (CV) risk. Aleglitazar is a dual peroxisome proliferator–activated receptor α/γ agonist with favorable insulin-sensitizing and glucose-lowering actions, favorable effects on blood lipids, and an acceptable safety profile in short-time studies. Therefore, it was hypothesized that aleglitazar would reduce CV morbidity and mortality in patients with T2D mellitus and prediabetes (defined as glycosylated hemoglobin ≥5.7% to <6.5%) with previous CV complications. Study design ALEPREVENT was a phase III, multicenter, randomized, double-blind, trial comparing aleglitazar 150 μg or placebo daily in patients with T2D or prediabetes with established, stable CV disease. The intended sample size was 19,000 with a primary efficacy measure of major adverse CV events. However, the trial was halted prematurely after 1,999 patients had been randomized because of futility and an unfavorable benefit risk ratio in another CV outcomes trial evaluating aleglitazar. Results At study termination after 58 ± 38 days of treatment, data had been collected from 1,996 patients (1,581 with T2D and 415 with pre-T2D). Despite the brief duration of treatment, aleglitazar induced favorable changes in glycosylated hemoglobin and blood lipids, similar for participants with T2D or prediabetes. However, compared with placebo, aleglitazar increased the incidence of hypoglycemia (86 vs 166; P < .0001), and muscular events (3 vs12; P = .012). Conclusions Even within a short duration of exposure, aleglitazar was associated with excess adverse events, corroborating the findings of a larger and longer trial in T2D. Coupled with the previous failure of several other peroxisome proliferator–activated receptor α/γ activators, this class now holds little promise for CV therapeutics.</description><identifier>ISSN: 0002-8703</identifier><identifier>EISSN: 1097-6744</identifier><identifier>DOI: 10.1016/j.ahj.2015.03.021</identifier><identifier>PMID: 26093872</identifier><identifier>CODEN: AHJOA2</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Cardiovascular ; Cardiovascular Diseases - complications ; Cardiovascular Diseases - prevention & control ; Cerebrovascular Disorders - complications ; Cholesterol ; Coronary Disease - complications ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Double-Blind Method ; Early Termination of Clinical Trials ; Female ; Glycated Hemoglobin A - metabolism ; Heart attacks ; Humans ; Hypoglycemia - chemically induced ; Hypoglycemic Agents - therapeutic use ; Male ; Metabolic disorders ; Middle Aged ; Mortality ; Myalgia - chemically induced ; Myocardial Infarction - complications ; Myocardial Infarction - prevention & control ; Myositis - chemically induced ; Oxazoles - therapeutic use ; Peripheral Arterial Disease - complications ; PPAR alpha - agonists ; PPAR gamma - agonists ; Prediabetic State - complications ; Prediabetic State - drug therapy ; Prediabetic State - metabolism ; Stroke - complications ; Stroke - prevention & control ; Thiophenes - therapeutic use ; Treatment Outcome</subject><ispartof>The American heart journal, 2015-07, Vol.170 (1), p.117-122</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jul 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c544t-131ad3c47f91262dc4c309e9cf5653df1416147a512ad6cb3cbf778a50203f133</citedby><cites>FETCH-LOGICAL-c544t-131ad3c47f91262dc4c309e9cf5653df1416147a512ad6cb3cbf778a50203f133</cites><orcidid>0000-0002-9887-3736</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002870315001969$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26093872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:131463782$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Erdmann, Erland, MD</creatorcontrib><creatorcontrib>Califf, Robert, MD</creatorcontrib><creatorcontrib>Gerstein, Hertzel C., MD</creatorcontrib><creatorcontrib>Malmberg, Klas, MD</creatorcontrib><creatorcontrib>Ruilope, Luis, MD</creatorcontrib><creatorcontrib>Schwartz, Gregory G., MD</creatorcontrib><creatorcontrib>Wedel, Hans, MD</creatorcontrib><creatorcontrib>Volz, Dietmar, MD</creatorcontrib><creatorcontrib>Ditmarsch, Marc, MD</creatorcontrib><creatorcontrib>Svensson, Anders, MD</creatorcontrib><creatorcontrib>Bengus, Monica, MD</creatorcontrib><title>Effects of the dual peroxisome proliferator–activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes</title><title>The American heart journal</title><addtitle>Am Heart J</addtitle><description>Background Insulin-resistant states, including type 2 diabetes (T2D) and prediabetes, are associated with elevated cardiovascular (CV) risk. Aleglitazar is a dual peroxisome proliferator–activated receptor α/γ agonist with favorable insulin-sensitizing and glucose-lowering actions, favorable effects on blood lipids, and an acceptable safety profile in short-time studies. Therefore, it was hypothesized that aleglitazar would reduce CV morbidity and mortality in patients with T2D mellitus and prediabetes (defined as glycosylated hemoglobin ≥5.7% to <6.5%) with previous CV complications. Study design ALEPREVENT was a phase III, multicenter, randomized, double-blind, trial comparing aleglitazar 150 μg or placebo daily in patients with T2D or prediabetes with established, stable CV disease. The intended sample size was 19,000 with a primary efficacy measure of major adverse CV events. However, the trial was halted prematurely after 1,999 patients had been randomized because of futility and an unfavorable benefit risk ratio in another CV outcomes trial evaluating aleglitazar. Results At study termination after 58 ± 38 days of treatment, data had been collected from 1,996 patients (1,581 with T2D and 415 with pre-T2D). Despite the brief duration of treatment, aleglitazar induced favorable changes in glycosylated hemoglobin and blood lipids, similar for participants with T2D or prediabetes. However, compared with placebo, aleglitazar increased the incidence of hypoglycemia (86 vs 166; P < .0001), and muscular events (3 vs12; P = .012). Conclusions Even within a short duration of exposure, aleglitazar was associated with excess adverse events, corroborating the findings of a larger and longer trial in T2D. Coupled with the previous failure of several other peroxisome proliferator–activated receptor α/γ activators, this class now holds little promise for CV therapeutics.</description><subject>Aged</subject><subject>Cardiovascular</subject><subject>Cardiovascular Diseases - complications</subject><subject>Cardiovascular Diseases - prevention & control</subject><subject>Cerebrovascular Disorders - complications</subject><subject>Cholesterol</subject><subject>Coronary Disease - complications</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Double-Blind Method</subject><subject>Early Termination of Clinical Trials</subject><subject>Female</subject><subject>Glycated Hemoglobin A - metabolism</subject><subject>Heart attacks</subject><subject>Humans</subject><subject>Hypoglycemia - chemically induced</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Male</subject><subject>Metabolic disorders</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Myalgia - chemically induced</subject><subject>Myocardial Infarction - complications</subject><subject>Myocardial Infarction - prevention & control</subject><subject>Myositis - chemically induced</subject><subject>Oxazoles - therapeutic use</subject><subject>Peripheral Arterial Disease - complications</subject><subject>PPAR alpha - agonists</subject><subject>PPAR gamma - agonists</subject><subject>Prediabetic State - complications</subject><subject>Prediabetic State - drug therapy</subject><subject>Prediabetic State - metabolism</subject><subject>Stroke - complications</subject><subject>Stroke - prevention & control</subject><subject>Thiophenes - therapeutic use</subject><subject>Treatment Outcome</subject><issn>0002-8703</issn><issn>1097-6744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9ks1uEzEQxy0EoiHwAFyQJS5cNvhrvWshIVWlfEiVOFDOluMdE6eb7GJ7W8KJN-DAG_IkTJRQpB44eTz6zX888zchTzlbcMb1y_XCrdYLwXi9YHLBBL9HZpyZptKNUvfJjDEmqrZh8oQ8ynmNVy1a_ZCcCM2MbBsxIz_PQwBfMh0CLSug3eR6OkIavsU8bICOaehjgOTKkH7_-OV8ideuQEcTeBgxSY-pfdTDlz4W990lGrd0dCXCFqVvYlnRy90IVNA30S2hQKYb6JGdsHHCJtAd84_Jg-D6DE-O55x8fnt-efa-uvj47sPZ6UXla6VKxSV3nfSqCYYLLTqvvGQGjA-1rmUXuOKaq8bVXLhO-6X0y9A0rauZYDJwKeekOujmGxinpR1T3Li0s4OL9pi6wggsKmhlkH9x4HEhXyfIxW5i9jiD28IwZcu1YVq1ArvPyfM76HqY0hanQao1sjZKaqT4gfJpyDlBuH0CZ3bvrl1bdNfu3bVMWnQXa54dlaflBrrbir92IvDqAACu7jpCstmjBx7Xi34V2w3xv_Kv71T7Pm6jd_0V7CD_m8JmYZn9tP9e-9_Fa8a40Ub-ATd7zS8</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Erdmann, Erland, MD</creator><creator>Califf, Robert, MD</creator><creator>Gerstein, Hertzel C., MD</creator><creator>Malmberg, Klas, MD</creator><creator>Ruilope, Luis, MD</creator><creator>Schwartz, Gregory G., MD</creator><creator>Wedel, Hans, MD</creator><creator>Volz, Dietmar, MD</creator><creator>Ditmarsch, Marc, MD</creator><creator>Svensson, Anders, MD</creator><creator>Bengus, Monica, MD</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>3V.</scope><scope>7QO</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><orcidid>https://orcid.org/0000-0002-9887-3736</orcidid></search><sort><creationdate>20150701</creationdate><title>Effects of the dual peroxisome proliferator–activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes</title><author>Erdmann, Erland, MD ; Califf, Robert, MD ; Gerstein, Hertzel C., MD ; Malmberg, Klas, MD ; Ruilope, Luis, MD ; Schwartz, Gregory G., MD ; Wedel, Hans, MD ; Volz, Dietmar, MD ; Ditmarsch, Marc, MD ; Svensson, Anders, MD ; Bengus, Monica, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-131ad3c47f91262dc4c309e9cf5653df1416147a512ad6cb3cbf778a50203f133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Cardiovascular</topic><topic>Cardiovascular Diseases - complications</topic><topic>Cardiovascular Diseases - prevention & control</topic><topic>Cerebrovascular Disorders - complications</topic><topic>Cholesterol</topic><topic>Coronary Disease - complications</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Double-Blind Method</topic><topic>Early Termination of Clinical Trials</topic><topic>Female</topic><topic>Glycated Hemoglobin A - metabolism</topic><topic>Heart attacks</topic><topic>Humans</topic><topic>Hypoglycemia - chemically induced</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Male</topic><topic>Metabolic disorders</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Myalgia - chemically induced</topic><topic>Myocardial Infarction - complications</topic><topic>Myocardial Infarction - prevention & control</topic><topic>Myositis - chemically induced</topic><topic>Oxazoles - therapeutic use</topic><topic>Peripheral Arterial Disease - complications</topic><topic>PPAR alpha - agonists</topic><topic>PPAR gamma - agonists</topic><topic>Prediabetic State - complications</topic><topic>Prediabetic State - drug therapy</topic><topic>Prediabetic State - metabolism</topic><topic>Stroke - complications</topic><topic>Stroke - prevention & control</topic><topic>Thiophenes - therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Erdmann, Erland, MD</creatorcontrib><creatorcontrib>Califf, Robert, MD</creatorcontrib><creatorcontrib>Gerstein, Hertzel C., MD</creatorcontrib><creatorcontrib>Malmberg, Klas, MD</creatorcontrib><creatorcontrib>Ruilope, Luis, MD</creatorcontrib><creatorcontrib>Schwartz, Gregory G., MD</creatorcontrib><creatorcontrib>Wedel, Hans, MD</creatorcontrib><creatorcontrib>Volz, Dietmar, MD</creatorcontrib><creatorcontrib>Ditmarsch, Marc, MD</creatorcontrib><creatorcontrib>Svensson, Anders, MD</creatorcontrib><creatorcontrib>Bengus, Monica, MD</creatorcontrib><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>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>The American heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Erdmann, Erland, MD</au><au>Califf, Robert, MD</au><au>Gerstein, Hertzel C., MD</au><au>Malmberg, Klas, MD</au><au>Ruilope, Luis, MD</au><au>Schwartz, Gregory G., MD</au><au>Wedel, Hans, MD</au><au>Volz, Dietmar, MD</au><au>Ditmarsch, Marc, MD</au><au>Svensson, Anders, MD</au><au>Bengus, Monica, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of the dual peroxisome proliferator–activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes</atitle><jtitle>The American heart journal</jtitle><addtitle>Am Heart J</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>170</volume><issue>1</issue><spage>117</spage><epage>122</epage><pages>117-122</pages><issn>0002-8703</issn><eissn>1097-6744</eissn><coden>AHJOA2</coden><abstract>Background Insulin-resistant states, including type 2 diabetes (T2D) and prediabetes, are associated with elevated cardiovascular (CV) risk. Aleglitazar is a dual peroxisome proliferator–activated receptor α/γ agonist with favorable insulin-sensitizing and glucose-lowering actions, favorable effects on blood lipids, and an acceptable safety profile in short-time studies. Therefore, it was hypothesized that aleglitazar would reduce CV morbidity and mortality in patients with T2D mellitus and prediabetes (defined as glycosylated hemoglobin ≥5.7% to <6.5%) with previous CV complications. Study design ALEPREVENT was a phase III, multicenter, randomized, double-blind, trial comparing aleglitazar 150 μg or placebo daily in patients with T2D or prediabetes with established, stable CV disease. The intended sample size was 19,000 with a primary efficacy measure of major adverse CV events. However, the trial was halted prematurely after 1,999 patients had been randomized because of futility and an unfavorable benefit risk ratio in another CV outcomes trial evaluating aleglitazar. Results At study termination after 58 ± 38 days of treatment, data had been collected from 1,996 patients (1,581 with T2D and 415 with pre-T2D). Despite the brief duration of treatment, aleglitazar induced favorable changes in glycosylated hemoglobin and blood lipids, similar for participants with T2D or prediabetes. However, compared with placebo, aleglitazar increased the incidence of hypoglycemia (86 vs 166; P < .0001), and muscular events (3 vs12; P = .012). Conclusions Even within a short duration of exposure, aleglitazar was associated with excess adverse events, corroborating the findings of a larger and longer trial in T2D. Coupled with the previous failure of several other peroxisome proliferator–activated receptor α/γ activators, this class now holds little promise for CV therapeutics.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26093872</pmid><doi>10.1016/j.ahj.2015.03.021</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-9887-3736</orcidid></addata></record> |
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| subjects | Aged Cardiovascular Cardiovascular Diseases - complications Cardiovascular Diseases - prevention & control Cerebrovascular Disorders - complications Cholesterol Coronary Disease - complications Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Double-Blind Method Early Termination of Clinical Trials Female Glycated Hemoglobin A - metabolism Heart attacks Humans Hypoglycemia - chemically induced Hypoglycemic Agents - therapeutic use Male Metabolic disorders Middle Aged Mortality Myalgia - chemically induced Myocardial Infarction - complications Myocardial Infarction - prevention & control Myositis - chemically induced Oxazoles - therapeutic use Peripheral Arterial Disease - complications PPAR alpha - agonists PPAR gamma - agonists Prediabetic State - complications Prediabetic State - drug therapy Prediabetic State - metabolism Stroke - complications Stroke - prevention & control Thiophenes - therapeutic use Treatment Outcome |
| title | Effects of the dual peroxisome proliferator–activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes |
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