Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events

被引：345

作者：

Holman, Rury R. ^{[1
]}

Haffner, Steven M. ^{[4
]}

McMurray, John J. ^{[2
]}

Bethel, M. Angelyn ^{[1
,5
]}

Holzhauer, Bjoern ^{[9
]}

Hua, Tsushung A. ^{[12
]}

Belenkov, Yuri ^{[13
]}

Boolell, Mitradev ^{[9
]}

Buse, John B. ^{[7
,8
]}

Buckley, Brendan M. ^{[14
]}

Chacra, Antonio R. ^{[15
]}

Chiang, Fu-Tien ^{[16
]}

Charbonnel, Bernard ^{[17
]}

Chow, Chun-Chung ^{[18
]}

Davies, Melanie J. ^{[3
]}

Deedwania, Prakash ^{[20
,21
]}

Diem, Peter ^{[10
,11
]}

Einhorn, Daniel ^{[22
,23
]}

Fonseca, Vivian ^{[24
]}

Fulcher, Gregory R. ^{[26
]}

Gaciong, Zbigniew ^{[28
]}

Gaztambide, Sonia ^{[29
]}

Giles, Thomas ^{[25
]}

Horton, Edward ^{[30
]}

Ilkova, Hasan ^{[31
]}

Jenssen, Trond ^{[32
,33
]}

Kahn, Steven E. ^{[34
,35
]}

Krum, Henry ^{[27
]}

Laakso, Markku ^{[36
,37
]}

Leiter, Lawrence A. ^{[40
]}

Levitt, Naomi S. ^{[41
]}

Mareev, Viacheslav ^{[13
]}

Martinez, Felipe ^{[42
]}

Masson, Chantal ^{[9
]}

Mazzone, Theodore ^{[45
]}

Meaney, Eduardo ^{[46
]}

Nesto, Richard ^{[47
]}

Pan, Changyu ^{[19
]}

Prager, Rudolf ^{[48
]}

Raptis, Sotirios A. ^{[49
]}

Rutten, Guy E. H. M. ^{[50
]}

Sandstroem, Herbert ^{[51
]}

Schaper, Frank ^{[52
]}

Scheen, Andre ^{[53
,54
]}

Schmitz, Ole ^{[55
,56
]}

Sinay, Isaac ^{[43
]}

Soska, Vladimir ^{[58
,59
]}

Stender, Steen ^{[57
]}

Tamas, Gyula ^{[60
]}

Tognoni, Gianni ^{[61
]}

机构：

[1] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[2] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland

[3] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England

[4] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA

[5] Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA

[6] Duke Univ, Duke Translat Med Inst, Durham, NC 27706 USA

[7] Univ N Carolina, Sch Med, Div Gen Med, Chapel Hill, NC USA

[8] Univ N Carolina, Sch Med, Clin Epidemiol & Diabet Care Ctr, Chapel Hill, NC USA

[9] Novartis Pharmaceut, Basel, Switzerland

[10] Univ Hosp Bern, Inselspital, Div Endocrinol Diabet & Clin Nutr, CH-3010 Bern, Switzerland

[11] Univ Bern, Bern, Switzerland

[12] Novartis Pharmaceut, E Hanover, NJ USA

[13] Moscow MV Lomonosov State Univ, Moscow 117234, Russia

[14] Natl Univ Ireland Univ Coll Cork, Cork, Ireland

[15] Univ Fed Sao Paulo, Sao Paulo, Brazil

[16] Natl Taiwan Univ Hosp, Dept Cardiol, Taipei, Taiwan

[17] Univ Hosp, Dept Endocrinol, Nantes, France

[18] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China

[19] 301 Hosp, Dept Endocrinol, Beijing, Peoples R China

[20] Calif State Univ Fresno, San Francisco Program Fresno, Div Cardiol, Fresno, CA 93740 USA

[21] VA Cent Calif Hlth Care Syst, Fresno, CA USA

[22] Univ Calif San Diego, La Jolla, CA 92093 USA

[23] Scripps Whittier Diabet Inst, La Jolla, CA USA

[24] Tulane Univ, Sch Med, Dept Endocrinol, New Orleans, LA 70112 USA

[25] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA

[26] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia

[27] Monash Univ, Alfred Hosp, Clin Pharmacol Unit, Dept Epidemiol & Prevent Med, Prahran, Vic, Australia

[28] Warsaw Med Univ, Dept Internal Med Hypertens & Vasc Dis, Warsaw, Poland

[29] Hosp Univ Cruces, Dept Endocrinol, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Baracaldo, Spain

[30] Joslin Diabet Ctr, Boston, MA 02215 USA

[31] Istanbul Univ, Dept Diabet Endocrinol & Metab, Istanbul, Turkey

[32] Oslo Univ Hosp, Rikshosp, Oslo Inst Clin Med, Tromso, Norway

[33] Univ Tromso, Tromso, Norway

[34] VA Puget Sound Hlth Care Syst, Seattle, WA USA

[35] Univ Washington, Seattle, WA 98195 USA

[36] Univ Kuopio, FIN-70211 Kuopio, Finland

[37] Kuopio Univ Hosp, SF-70210 Kuopio, Finland

[38] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland

[39] S Ostrobothnia Cent Hosp, Seinajoki, Finland

[40] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada

[41] Univ Cape Town, Dept Med, Endocrine Unit, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa

[42] Natl Univ Cordoba, Cordoba, Spain

[43] Univ Buenos Aires, Inst Cardiovasc Buenos Aires, Buenos Aires, DF, Argentina

[44] Univ Buenos Aires, Hypertens Unit, Div Cardiol, Argerich Hosp, Buenos Aires, DF, Argentina

[45] Univ Illinois, Dept Diabet & Metab, Chicago, IL USA

[46] Hosp 10 Octubre, Inst Seguridad & Serv Sociales Trabajadores Estad, Mexico City, DF, Mexico

[47] Lahey Clin Fdn, Burlington, MA USA

[48] Krankenhaus Hietzing Neurolog, Zentrum Rosenhugel, Hietzig Hosp, Vienna, Austria

[49] Attikon Univ Hosp, Hellen Natl Diabet Ctr, Dept Internal Med Endocrinol & Diabetol 2, Athens, Greece

[50] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 362卷 / 16期

关键词：

IMPAIRED GLUCOSE-TOLERANCE; INSULIN-SECRETION; LIFE-STYLE; PREVENTION; MELLITUS; NIDDM; ACARBOSE; DISEASE; TRIAL; DIET;

D O I：

10.1056/NEJMoa1001122

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.)

引用

页码：1463 / 1476

页数：14

共 29 条

[1] The metabolic syndrome - a new worldwide definition [J].

Alberti, KGMM ;

Zimmet, P ;

Shaw, J .

LANCET, 2005, 366 (9491) :1059-1062

[2]

Alberti KGMM, 1998, DIABETIC MED, V15, P539, DOI 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO

[3]

2-S

[4]

[Anonymous], LANCET

[5] Determining the most appropriate components for a composite clinical trial outcome [J].

Bethel, M. Angelyn ;

Holman, Rury ;

Haffner, Steven M. ;

Califf, Robert M. ;

Huntsman-Labed, Alice ;

Hua, Tsushung A. ;

McMurray, John .

AMERICAN HEART JOURNAL, 2008, 156 (04) :633-640

[6]

Borch-Johnsen K, 1999, LANCET, V354, P617

[7] 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study [J].

Bray, G. A. ;

Chatellier, A. ;

Duncan, C. ;

Greenway, F. L. ;

Levy, E. ;

Ryan, D. H. ;

Polonsky, K. S. ;

Tobian, J. ;

Ehrmann, D. ;

Matulik, M. J. ;

Clark, B. ;

Czech, K. ;

DeSandre, C. ;

Hilbrich, R. ;

McNabb, W. ;

Semenske, A. R. ;

Goldstein, B. J. ;

Smith, K. A. ;

Wildman, W. ;

Pepe, C. ;

Goldberg, R. B. ;

Calles, J. ;

Ojito, J. ;

Castillo-Florez, S. ;

Florez, H. J. ;

Giannella, A. ;

Lara, O. ;

Veciana, B. ;

Haffner, S. M. ;

Montez, M. G. ;

Lorenzo, C. ;

Martinez, A. ;

Hamman, R. F. ;

Testaverde, L. ;

Bouffard, A. ;

Dabelea, D. ;

Jenkins, T. ;

Lenz, D. ;

Perreault, L. ;

Price, D. W. ;

Steinke, S. C. ;

Horton, E. S. ;

Poirier, C. S. ;

Swift, K. ;

Caballero, E. ;

Jackson, S. D. ;

Lambert, L. ;

Lawton, K. E. ;

Ledbury, S. ;

Kahn, S. E. .

LANCET, 2009, 374 (9702) :1677-1686

[8] Prevention of diabetes and cardiovascular' disease in patients with impaired glucose tolerance: Rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial [J].

Califf, Robert M. ;

Boolell, Mitradev ;

Haffner, Steven M. ;

Bethel, M. Angelyn ;

McMurray, John ;

Duggal, Anil ;

Holman, Rury R. .

AMERICAN HEART JOURNAL, 2008, 156 (04) :623-632

[9] Acarbose for prevention of type 2 diabetes mellitus: the STOPNIDDM randomised trial [J].

Chiasson, JL ;

Josse, RG ;

Gomis, R ;

Hanefeld, M ;

Karasik, A ;

Laakso, M .

LANCET, 2002, 359 (9323) :2072-2077

[10] Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance - The STOP-NIDDM Ttrial [J].

Chiasson, JL ;

Josse, RG ;

Gomis, R ;

Hanefeld, M ;

Karasik, A ;

Laakso, M .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 290 (04) :486-494

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