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 origi-nally 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, nei-ther strategy reduced all-cause, cancer, or cardiovascular mortality rates.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2775-2782 |
| Number of pages | 8 |
| Journal | Diabetes care |
| Volume | 44 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2021 |
Funding
Acknowledgments. The Diabetes Prevention Program Research Group Research Group gratefully acknowledges the commitment and dedication of the participants of DPP and DPPOS. Funding. Research reported in this publication was supported by the NIDDK of the NIH under award numbers U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400, through providing funding during DPP and DPPOS to the clinical centers and the Coordinating Center for the design and conduct of the study, and through collection, management, analysis, and interpretation of the data. Funding was also provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Office of Research on Women’s Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Merck KGaA provided medication for DPPOS. DPP/DPPOS have also received donated materials, equipment, or medicines for concomitant conditions from Bristol-Myers Squibb, Parke-Davis, and LifeScan, Health o Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck and Co., Nike Sports Marketing, SlimFast, and The Quaker Oats Company. The sponsor of this study was represented on the Steering Committee and played a part in study design, how the study was done, and publication. Research reported in this publication was supported by the NIDDK of the NIH under award numbers U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400, through providing funding during DPP and DPPOS to the clinical centers and the Coordinating Center for the design and conduct of the study, and through collection, management, analysis, and interpretation of the data. Funding was also provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Office of Research on Women?s Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Merck KGaA provided medication for DPPOS. DPP/DPPOS have also received donated materials, equipment, or medi-cines for concomitant conditions from Bristol-Myers Squibb, Parke-Davis, and LifeScan, Health o Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck and Co., Nike Sports Mar-keting, SlimFast, and The Quaker Oats Company. The sponsor of this study was represented on the Steering Committee and played a part in study design, how the study was done, and publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. All authors in the writing group had access to all data. The opinions expressed are those of the study group and do not necessarily reflect the views of the funding agencies. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. All authors in the writing group had access to all data. The opinions expressed are those of the study group and do not necessarily reflect the views of the funding agencies. Duality of Interest. K.M.G. received research grants from AstraZeneca and BioKier. McKes-son BioServices, Matthews Media Group, and Henry M. Jackson Foundation for the Advancement of Military Medicine provided support services under subcontract with the Coordinating Center. No other potential conflicts of interest relevant to this article were reported. Author Contributions. C.G.L. and M.T. wrote the manuscript and researched the data. B.H., D.D., K.M.G., P.P., E.J.B., W.C.K., and J.P.C. researched data, edited and reviewed the manuscript, and contributed to discussion. D.E., L.F., X.P., and A.W. reviewed and edited the manuscript. M.T. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Advanced and Specialized Nursing
