Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study
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- Christine G. Lee
- Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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- Brandy Heckman-Stoddard
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD
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- Dana Dabelea
- Department of Epidemiology and Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
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- Kishore M. Gadde
- Pennington Biomedical Research Center, Baton Rouge, LA
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- David Ehrmann
- University of Chicago, Chicago, IL
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- Leslie Ford
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD
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- Philip Prorok
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD
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- Edward J. Boyko
- Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle
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- Xavier Pi-Sunyer
- Columbia University Irving Medical Center, New York, New York
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- Amisha Wallia
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
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- William C. Knowler
- Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
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- Jill P. Crandall
- Division of Endocrinology and Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY
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- Marinella Temprosa
- Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC
説明
<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>To determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>From 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Over a median of 21 years (interquartile range 20–21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.</jats:p> </jats:sec>
収録刊行物
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- Diabetes Care
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Diabetes Care 44 (12), 2775-2782, 2021-10-25
American Diabetes Association