Effect of nateglinide on the incidence of diabetes and cardiovascular events
NAVIGATOR Study Group, Rury R Holman, Steven M Haffner, John J McMurray, M Angelyn Bethel, Björn Holzhauer, Tsushung A Hua, Yuri Belenkov, Mitradev Boolell, John B Buse, Brendan M Buckley, Antonio R Chacra, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, Viacheslav Mareev, Felipe Martinez, Chantal Masson, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert M Califf, Robert M Califf, Rury R Holman, Mitradev Boolell, Steven M Haffner, John J McMurray, Anil Duggal, M Angelyn Bethel, Robert M Califf, Steven M Haffner, Rury R Holman, John J McMurray, Antonio Gotto, Aldo Maggioni, Eberhard Standl, Joel Verter, Bernard Zinman, Yuri Belenkov, John B Buse, Brendan M Buckley, Antonio R Chacra, Robert M Califf, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Steven M Haffner, Rury R Holman, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, John J McMurray, Viacheslav Mareev, Felipe Martinez, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert J Heine, Markolf Hanefeld, Mustaffa Embong, Josef Drzewoski, J Eriksson, Clicerio González-Villalpando, Robert Ratner, Andrew Boulton, Nick J Wareham, Sorin Bresner, Arman Askari, Venugopal Menon, Michael Chen, Anjli Maroo, Oussama Wazni, Khaled Ziada, Matthews Chacko, Michael McWilliams, Vivek Rajagopal, Stephen Gimple, Mateen Akhtar, Matthew Casey Becker, John Galla, Deborah Kwon, Kellan Ashley, Cathy Sila, Irene Katza, Narcis Pasca, Lori Blashford, Kim J Brown, Mary Del Valle, Mary J Heckman, Andreea Mocanu, Kathleen K Sankovic, Wendy Sarver, Christine Shaffer, NAVIGATOR Study Group, Rury R Holman, Steven M Haffner, John J McMurray, M Angelyn Bethel, Björn Holzhauer, Tsushung A Hua, Yuri Belenkov, Mitradev Boolell, John B Buse, Brendan M Buckley, Antonio R Chacra, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, Viacheslav Mareev, Felipe Martinez, Chantal Masson, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert M Califf, Robert M Califf, Rury R Holman, Mitradev Boolell, Steven M Haffner, John J McMurray, Anil Duggal, M Angelyn Bethel, Robert M Califf, Steven M Haffner, Rury R Holman, John J McMurray, Antonio Gotto, Aldo Maggioni, Eberhard Standl, Joel Verter, Bernard Zinman, Yuri Belenkov, John B Buse, Brendan M Buckley, Antonio R Chacra, Robert M Califf, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Steven M Haffner, Rury R Holman, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, John J McMurray, Viacheslav Mareev, Felipe Martinez, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert J Heine, Markolf Hanefeld, Mustaffa Embong, Josef Drzewoski, J Eriksson, Clicerio González-Villalpando, Robert Ratner, Andrew Boulton, Nick J Wareham, Sorin Bresner, Arman Askari, Venugopal Menon, Michael Chen, Anjli Maroo, Oussama Wazni, Khaled Ziada, Matthews Chacko, Michael McWilliams, Vivek Rajagopal, Stephen Gimple, Mateen Akhtar, Matthew Casey Becker, John Galla, Deborah Kwon, Kellan Ashley, Cathy Sila, Irene Katza, Narcis Pasca, Lori Blashford, Kim J Brown, Mary Del Valle, Mary J Heckman, Andreea Mocanu, Kathleen K Sankovic, Wendy Sarver, Christine Shaffer
Abstract
Background: The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown.
Methods: In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization.
Results: After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia.
Conclusions: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)
2010 Massachusetts Medical Society
Source: PubMed