{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Green JB"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NIGMS NIH HHS"],"pagination":["993-1003"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10978227"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["149(13)"],"pubmed_abstract":["<h4>Background</h4>Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes. The effects of glucose-lowering medications on cardiovascular outcomes in individuals with type 2 diabetes and low cardiovascular risk are unclear. We investigated cardiovascular outcomes by treatment group in participants randomly assigned to insulin glargine, glimepiride, liraglutide, or sitagliptin, added to baseline metformin, in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study).<h4>Methods</h4>A total of 5047 participants with a mean±SD age of 57.2±10.0 years, type 2 diabetes duration of 4.0±2.7 years, and low baseline prevalence of cardiovascular disease (myocardial infarction, 5.1%; cerebrovascular accident, 2.0%) were followed for a median of 5 years. Prespecified outcomes included between-group time-to-first event analyses of MACE-3 (composite of major adverse cardiovascular events: cardiovascular death, myocardial infarction, and stroke), MACE-4 (MACE-3+unstable angina requiring hospitalization or revascularization), MACE-5 (MACE-4+coronary revascularization), MACE-6 (MACE-5+hospitalization for heart failure), and the individual components. MACE outcomes and hospitalization for heart failure in the liraglutide-treated group were compared with the other groups combined using Cox proportional hazards models. MACE-6 was also analyzed as recurrent events using a proportional rate model to compare all treatment groups.<h4>Results</h4>We observed no statistically significant differences in the cumulative incidence of first MACE-3, MACE-4, MACE-5, or MACE-6, or their individual components, by randomized treatment group. However, when compared with the other treatment groups combined, the liraglutide-treated group had a significantly lower risk of MACE-5 (adjusted hazard ratio, 0.70 [95% CI, 0.54-0.91]; <i>P</i>=0.021), MACE-6 (adjusted hazard ratio, 0.70 [95% CI, 0.55-0.90]; <i>P</i>=0.021), and hospitalization for heart failure (adjusted hazard ratio, 0.49 [95% CI, 0.28-0.86]; <i>P</i>=0.022). Compared with the liraglutide group, significantly higher rates of recurrent MACE-6 events occurred in the groups treated with glimepiride (rate ratio, 1.61 [95% CI, 1.13-2.29]) or sitagliptin (rate ratio 1.75; [95% CI, 1.24-2.48]).<h4>Conclusions</h4>This comparative effectiveness study of a contemporary cohort of adults with type 2 diabetes, largely without established cardiovascular disease, suggests that liraglutide treatment may reduce the risk of cardiovascular events in patients at relatively low risk compared with other commonly used glucose-lowering medications.<h4>Registration</h4>URL: https://www.clinicaltrials.gov; Unique identifier: NCT01794143."],"journal":["Circulation"],"pubmed_title":["Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study)."],"pmcid":["PMC10978227"],"funding_grant_id":["UL1 TR001102","UM1 TR004528","UL1 TR002378","UL1 TR002537","UL1 TR001425","UL1 TR002535","UL1 TR000439","UL1 TR001108","UL1 TR001449","UL1 TR001409","P30 DK020572","UL1 TR002243","P30 DK092926","UL1 TR002489","UL1 TR002345","UL1 TR002541","UL1 TR002548","P30 DK017047","U54 GM104940","UL1 TR000445","UL1 TR002529","U34 DK088043","P30 DK072476","U01 DK098246","P30 DK079626","P30 DK020541","UL1 TR000170"],"pubmed_authors":["Estrada L","Pucchetti B","Schield E","Petrovitch H","Utzschneider KM","Alfano L","Rassouli N","Ressing A","Rhothisen S","Kuechenmeister L","Ngo L","DeManbey A","Bahtiyar G","Burgess E","Schnurr-Breen L","Magee M","Cherrington AL","Mech M","Maher-Albertelli M","Gonzalez Hattery E","Person S","Oropesa-Gonzalez L","Waltje A","Ballentine-Cargill K","Hurtado M","Satterwhite BM","Young T","Falck-Ytter C","Juarez D","Young L","Sanders C","Tsovian M","Montgomery BK","Howard D","Karshner T","Groessl E","Ye W","Gliwa A","Herson M","Jenkins V","Soni L","Frances S","Salam M","Kissel S","Ross A","Curtis JM","Morton L","Yamashita D","Min DJ","McGill JB","Henry R","Morton S","Kirpitch A","Joarder F","Scripsick E","Boeder S","Montes G","Passi R","Ayala R","Hinkle N","Chatterjee R","Broadwater L","Yepes M","Coe M","Chionh K","Brown-Friday J","Ellis E","Nelson R","Dostou J","Assuras S","Loveland A","Martinez J","Ismail HM","Penaloza R","Buse JB","Olson D","Lachin JM","Sanders-Jones C","Myers J","Scrymgeour A","Panos E","Almeida H","Hsia DS","Tamborlane W","Liu H","Bebu I","Arnold K","Johnson M","Gumpel K","Magenheimer E","Phillips LS","Gramzinski MR","Maggio C","Pokharel Y","Huminik J","Harindhanavudhi T","Alguard M","Meigs J","Bremer AA","Killean T","Khalid M","Schell K","Kleeberger K","Perez M","Goodhall L","Lukin J","Aby-Daniel D","Bergenstal R","El-Haqq Z","Martin D","McConnell J","Martin C","Marks J","Hernandez S","Cherian A","Gatcomb P","Stevens C","Dushkin A","Sanchez O","Castro E","Tripputi M","Suratt C","Pham K","Soliman EZ","Meiners V","Meiners R","Kringas P","Gildersleeve B","Hillery N","Burge M","Kahn SE","Krause-Steinrauf H","Alarcon-Casas Wright L","DeLue C","Tsai EC","Mwicigi F","Bule S","Inzucchi SE","Clifton MJ","Hurt S","Dyer D","Keasler L","Kirchhoff P","Younes N","GRADE Study Research Group","Bourgeois B","Ripley V","Taddese A","Osornio Walker L","Cook J","Nazarov S","McCullars S","Sacerdote A","Kersey K","Ahmann A","Kazemi E","Schade D","Feinglos MN","Boers J","Puttnam R","Sibymon M","Schroeder E","Goley A","Camp A","Verastiqui H","Craine JJ","Holloway L","Kononets MV","Ali Jamaleddin Ahmad F","Curtis M","Maggs S","Katona A","Tran T","Kiker L","Mudaliar S","Sanchez D","Mihalcea R","Trence DL","Florez HJ","Brantley P","Barzilay J","Morimoto V","Hernandez McGinnis D","Hollander P","Mishko MM","Warren S","Baker C","Balasubramanyam A","Hox SH","Agne A","Manandhar L","Kunkel S","Goidel R","Colosimo L","Costello J","McKee MD","Cuffee J","Largay JF","Machineni S","Pettus J","Backman M","Hollis B","Morehead F","Cersosimo E","Khan SA","Ishii RR","Wexler D","Broyles FE","Gao Y","Gabrielson D","Criscola J","Diaz E","Mullen M","Duran 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B","Griffith O","Pi-Sunyer FX","Banerji MA","Abdouch I","Yang S","Duran-Valdez E","Montosa A","Konerza W","Everett BM","O'Neal H","Friason C","Bojescu S","Cohen RM","Gonzalez de la Torre S","Gong X","Evans Kreider K","Newman C","Tsingine K","Saenger A","Crandall JP","Burton K","Iannone L","Thomassie A","Rasouli N","McGee P","Schweiger T","Riccio Veliz AK","King E","Puckett C","Mularski K","Tejada J","Jimenez J","Perez-Rosas V","Seipel K","Zimmer RP","Steffes M","Aroda V","Campbell C","Morales Gomez B","Fuller G","Pirics V","Kumar A","Ghioni D","Mather KJ"],"additional_accession":[]},"is_claimable":false,"name":"Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study).","description":"<h4>Background</h4>Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes. The effects of glucose-lowering medications on cardiovascular outcomes in individuals with type 2 diabetes and low cardiovascular risk are unclear. We investigated cardiovascular outcomes by treatment group in participants randomly assigned to insulin glargine, glimepiride, liraglutide, or sitagliptin, added to baseline metformin, in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study).<h4>Methods</h4>A total of 5047 participants with a mean±SD age of 57.2±10.0 years, type 2 diabetes duration of 4.0±2.7 years, and low baseline prevalence of cardiovascular disease (myocardial infarction, 5.1%; cerebrovascular accident, 2.0%) were followed for a median of 5 years. Prespecified outcomes included between-group time-to-first event analyses of MACE-3 (composite of major adverse cardiovascular events: cardiovascular death, myocardial infarction, and stroke), MACE-4 (MACE-3+unstable angina requiring hospitalization or revascularization), MACE-5 (MACE-4+coronary revascularization), MACE-6 (MACE-5+hospitalization for heart failure), and the individual components. MACE outcomes and hospitalization for heart failure in the liraglutide-treated group were compared with the other groups combined using Cox proportional hazards models. MACE-6 was also analyzed as recurrent events using a proportional rate model to compare all treatment groups.<h4>Results</h4>We observed no statistically significant differences in the cumulative incidence of first MACE-3, MACE-4, MACE-5, or MACE-6, or their individual components, by randomized treatment group. However, when compared with the other treatment groups combined, the liraglutide-treated group had a significantly lower risk of MACE-5 (adjusted hazard ratio, 0.70 [95% CI, 0.54-0.91]; <i>P</i>=0.021), MACE-6 (adjusted hazard ratio, 0.70 [95% CI, 0.55-0.90]; <i>P</i>=0.021), and hospitalization for heart failure (adjusted hazard ratio, 0.49 [95% CI, 0.28-0.86]; <i>P</i>=0.022). Compared with the liraglutide group, significantly higher rates of recurrent MACE-6 events occurred in the groups treated with glimepiride (rate ratio, 1.61 [95% CI, 1.13-2.29]) or sitagliptin (rate ratio 1.75; [95% CI, 1.24-2.48]).<h4>Conclusions</h4>This comparative effectiveness study of a contemporary cohort of adults with type 2 diabetes, largely without established cardiovascular disease, suggests that liraglutide treatment may reduce the risk of cardiovascular events in patients at relatively low risk compared with other commonly used glucose-lowering medications.<h4>Registration</h4>URL: https://www.clinicaltrials.gov; Unique identifier: NCT01794143.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-02T06:33:50.633Z","creation":"2026-04-15T03:15:27.547Z"},"accession":"S-EPMC10978227","cross_references":{"pubmed":["38344820"],"doi":["10.1161/circulationaha.123.066604","10.1161/CIRCULATIONAHA.123.066604"]}}