Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research` Rury R. Holman, MB, ChB, FRCP Professor of Diabetic Medicine Director, Diabetes Trials Unit, Oxford Robert M. Califf, MD, MACC Vice Chancellor for Clinical Research Donald F. Fortin Professor of Cardiology, Duke University Director, Duke Translational Medicine Institute
37
Embed
Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research` Rury R. Holman, MB, ChB, FRCP Professor of Diabetic Medicine Director, Diabetes.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research`
Rury R. Holman, MB, ChB, FRCP Professor of Diabetic Medicine
Director, Diabetes Trials Unit, Oxford
Robert M. Califf, MD, MACC Vice Chancellor for Clinical Research
Donald F. Fortin Professor of Cardiology, Duke University Director, Duke Translational Medicine Institute
For the NAVIGATOR Study Group
NAVIGATOR Trial Organization
Sponsored by Novartis Pharmaceuticals
Executive CommitteeTrial Oversight
Publications
Steering Committee43 Members
Data Monitoring Committee
Trial OperationsNovartis
Research Sites806 centers in 40 countries
Endpoint Committees
Rury Holman
Need to check this number!
Jonathan
Listing committee members is going to take at least several slides.
Primary Objective
To evaluate whether valsartan or nateglinide, in addition to lifestyle modification, can reduce the risk of diabetes and cardiovascular events in persons with impaired glucose tolerance (IGT) and either cardiovascular disease or risk factors for cardiovascular disease
Valsartan/Nateglinide(n=2316)
Nateglinide/Placebo(n=2329)
Valsartan/Placebo(n=2315)
Placebo/Placebo(n=2346)
NAVIGATOR 2 × 2 Factorial Design
• All subjects participated in a lifestyle modification program• Nateglinide 60 mg three times a day before meals • Valsartan 160 mg once a day
Na
teg
linid
e C
om
pa
rison
Valsartan Comparison
North America
2146
Asia-Pacific692
Africa153
Central & South America
1406
Europe4909
NAVIGATOR Global Enrollment
9306 patients
806 centers
40 countries
Major Inclusion CriteriaIGT* plus FPG ≥95 mg/dL (≥5.3 mmol/L) and
either CVD and age 50 yr or 1 risk factor for CVD and age 55 yr
*Impaired glucose tolerance according to ADA definition: Nathan DM et al, Diabetes Care, 2007
Coprimary Endpoints
• Incidence of diabetesFPG ≥126 mg/dL (≥7.0 mmol/L) and/or 2 hr PG ≥200 mg/dL (≥11.1 mmol/L), confirmed on OGTT within 12 weeks
• Extended cardiovascular outcomeCV death, nonfatal MI, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or unstable angina
• Core cardiovascular outcomeCV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure
Nateglinide Data
Meal
Saloranta C et al. Diabetes Care 2002;25:2141-2146
NAVIGATOR Pilot Study
Postprandial glucose lowering with nateglinide in IGT
In people with IGT and CV disease or risk factors, valsartan in addition to lifestyle modification leads to:– 14% relative (3.8% absolute) reduction in
the incidence of diabetes (median follow-up 5 yrs)
– Did not reduce the co-primary CV outcomes
Thoughts After NAVIGATOR
• We are in the midst of a global epidemic of obesity, diabetes, and associated cardiovascular disease.
• Many people with impaired glucose tolerance will develop diabetes in a short period of time, even with standard medical care.
• Lifestyle intervention remains the cornerstone of diabetes prevention and therapy for impaired glucose tolerance.
• We must continue to seek better pharmacological treatments while emphasizing exercise and weight control to prevent diabetes and its morbid and mortal consequences.
• NAVIGATOR demonstrates once again that the risks and benefits of therapies cannot be predicted accurately based on biology and intermediate measures, so they must be empirically demonstrated with proper RCTs
Robert M. Califf, MD reports receiving research grant support from Novartis Pharmaceuticals, Johnson & Johnson/Scios, Lilly, Merck, and Schering Plough, and consulting fees from Annenberg, Aterovax, Bayer/Ortho McNeil, BMS, Boehringer Ingelheim, GSK, WebMd/theheart.org, Johnson and Johnson/Scios, Kowa Research Institute, McKinsey & Company, Medtronic, Merck, Novartis Pharmaceuticals, Sanofi Aventis, and Schering Plough, and an equity position with NITROX, LLC. All personal income from industry relations is donated to non-profit entities. Dr. Califf's industry relations are kept up to date quarterly at www.dcri.org/coi.jsp.
Disclosures
Rury R. Holman MD, reports receiving grant support from Asahi Kasei Pharma, Bayer Healthcare, Bayer Schering Pharma, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Merck Serono, Novartis, Novo Nordisk, Pfizer, and Sanofi-Aventis, consulting fees from Amylin, Eli Lilly, GlaxoSmithKline, Merck, and Novartis, and lecture fees from Astella, Bayer, GlaxoSmithKline, King Pharmaceuticals, Eli Lilly, Merck, Merck Serono, Novo Nordisk, Takeda and Sanofi-Aventis.