학술논문
Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.
Document Type
Academic Journal
Author
Lee CG; Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD dppmail@bsc.gwu.edu.; Heckman-Stoddard B; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD.; Dabelea D; 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.; Gadde KM; Pennington Biomedical Research Center, Baton Rouge, LA.; Ehrmann D; University of Chicago, Chicago, IL.; Ford L; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD.; Prorok P; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD.; Boyko EJ; Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle.; Pi-Sunyer X; Columbia University Irving Medical Center, New York, New York.; Wallia A; Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.; Knowler WC; Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.; Crandall JP; Division of Endocrinology and Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY.; Temprosa M
Source
Publisher: American Diabetes Association Country of Publication: United States NLM ID: 7805975 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1935-5548 (Electronic) Linking ISSN: 01495992 NLM ISO Abbreviation: Diabetes Care Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: 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.
Research Design and Methods: 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.
Results: 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.
Conclusions: 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.
(© 2021 by the American Diabetes Association.)
Research Design and Methods: 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.
Results: 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.
Conclusions: 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.
(© 2021 by the American Diabetes Association.)