Long-term Study of Nateglinide+Valsartan to Prevent or Delay Type II Diabetes Mellitus and Cardiovascular Complications

Summary

This study is a test of the safety and effectiveness of two drugs, one for diabetes and one for hypertension, in keeping patients with high lab values of glucose from progressing to frank diabetes and developing cardiovascular complications. People in this study cannot have frank diabetes but are considered "borderline" based on blood tests. People in the study take none, one or both of the drugs and do not know which one(s) they are taking.

Timeline

Start

2002-01

Primary completion

2009-10

Completion

2009-10

Outcome

Mixed primary results

paper valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001 PMID 20228403 ↗

paper Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome PMID 20228403 ↗

paper assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. PMID 20228402 ↗

Publications

• Harumi Higuchi Dos Santos M, Sharma A, Sun JL, Pieper K, McMurray JJ, Holman RR, Lopes RD. International Variation in Outcomes Among People with Cardiovascular Disease or Cardiovascular Risk Factors and Impaired Glucose Tolerance: Insights from the NAVIGATOR Trial. J Am Heart Assoc. 2017 Jan 13;6(1):e003892. doi: 10.1161/JAHA.116.003892.
• Preiss D, Thomas LE, Wojdyla DM, Haffner SM, Gill JM, Yates T, Davies MJ, Holman RR, McMurray JJ, Califf RM, Kraus WE; NAVIGATOR Investigators. Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study. BMJ Open. 2015 Aug 14;5(8):e007901. doi: 10.1136/bmjopen-2015-007901.
• Katz M, Califf RM, Sun JL, McMurray JJ, Thomas L, Lopes RD. Venous thromboembolism and cardiovascular risk: results from the NAVIGATOR trial. Am J Med. 2015 Mar;128(3):297-302. doi: 10.1016/j.amjmed.2014.08.022. Epub 2014 Nov 20.
• Preiss D, Haffner SM, Thomas LE, Sun JL, Sattar N, Yates T, J Davies M, McMurray JJ, Holman RR, Califf RM, Kraus WE. Change in levels of physical activity after diagnosis of type 2 diabetes: an observational analysis from the NAVIGATOR study. Diabetes Obes Metab. 2014 Dec;16(12):1265-8. doi: 10.1111/dom.12320. Epub 2014 Jun 19.
• Huffman KM, Sun JL, Thomas L, Bales CW, Califf RM, Yates T, Davies MJ, Holman RR, McMurray JJ, Bethel MA, Tuomilehto J, Haffner SM, Kraus WE. Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: results from NAVIGATOR. Metabolism. 2014 Apr;63(4):554-61. doi: 10.1016/j.metabol.2014.01.002. Epub 2014 Jan 15.
• Yates T, Haffner SM, Schulte PJ, Thomas L, Huffman KM, Bales CW, Califf RM, Holman RR, McMurray JJ, Bethel MA, Tuomilehto J, Davies MJ, Kraus WE. Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis. Lancet. 2014 Mar 22;383(9922):1059-66. doi: 10.1016/S0140-6736(13)62061-9. Epub 2013 Dec 20.
• Shen L, Shah BR, Reyes EM, Thomas L, Wojdyla D, Diem P, Leiter LA, Charbonnel B, Mareev V, Horton ES, Haffner SM, Soska V, Holman R, Bethel MA, Schaper F, Sun JL, McMurray JJ, Califf RM, Krum H. Role of diuretics, beta blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013 Dec 9;347:f6745. doi: 10.1136/bmj.f6745.
• NAVIGATOR Study Group; McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamas G, Tognoni G, Tuomilehto J, Villamil AS, Vozar J, Califf RM. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010 Apr 22;362(16):1477-90. doi: 10.1056/NEJMoa1001121. Epub 2010 Mar 14.
• NAVIGATOR Study Group; Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamas G, Tognoni G, Tuomilehto J, Villamil AS, Vozar J, Califf RM. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010 Apr 22;362(16):1463-76. doi: 10.1056/NEJMoa1001122. Epub 2010 Mar 14.
• Krum H, McMurray JJ, Horton E, Gerlock T, Holzhauer B, Zuurman L, Haffner SM, Bethel MA, Holman RR, Califf RM. Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials. Cardiovasc Ther. 2010 Apr;28(2):124-32. doi: 10.1111/j.1755-5922.2010.00146.x. Epub 2010 Feb 23.
• Bethel MA, Deedwania P, Levitt NS, Schmitz O, Huntsman-Labed A, Califf RM, Haffner SM, Diem P; NAVIGATOR Study Group. Metabolic syndrome and alanine aminotransferase: a global perspective from the NAVIGATOR screening population. Diabet Med. 2009 Dec;26(12):1204-11. doi: 10.1111/j.1464-5491.2009.02864.x.
• Bethel MA, Holman R, Haffner SM, Califf RM, Huntsman-Labed A, Hua TA, McMurray J. Determining the most appropriate components for a composite clinical trial outcome. Am Heart J. 2008 Oct;156(4):633-40. doi: 10.1016/j.ahj.2008.05.018. Epub 2008 Jul 31.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Nateglinide	Small molecule	60 mg	Oral
Subject	Valsartan	Unknown	160 mg	Oral

Indications