TY - JOUR
T1 - Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up
T2 - The Diabetes Prevention Program Outcomes Study
AU - Diabetes Prevention Program Research Group
AU - Nathan, David M.
AU - Barrett-Connor, Elizabeth
AU - Crandall, Jill P.
AU - Edelstein, Sharon L.
AU - Goldberg, Ronald B.
AU - Horton, Edward S.
AU - Knowler, William C.
AU - Mather, Kieren J.
AU - Orchard, Trevor J.
AU - Pi-Sunyer, Xavier
AU - Schade, David
AU - Temprosa, Marinella
N1 - Funding Information:
The Research Group gratefully acknowledges the commitment and dedication of the Diabetes Prevention Program (DPP) and DPP Outcomes Study (DPPOS) participants. A complete list of centres, investigators, and staff can be found in the appendix . During the DPPOS, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the US National Institutes of Health (NIH) provided funding to the clinical centres and the coordinating centre for the design and conduct of the study, and collection, management, analysis, and interpretation of the data (U01 DK048489). 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 later the Clinical Translational Science Centers Programs of the National Center for Advancing Translational Sciences (NIH) and the Department of Veterans Affairs supported data collection at many of the clinical centres. Funding was also provided by the 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 Office of Research on Women's Health, the National Institute on Minority Health and Health Disparities, the US Centers for Disease Control and Prevention, and the American Diabetes Association. The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies. Industry contributors have had no role in the planning or conduct of the DPP and DPPOS, but Bristol-Myers Squibb and Parke-Davis provided additional funding and material support during the DPP, and Lipha (Merck-Sante) provided drugs and LifeScan donated materials during the DPP and DPPOS.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/11
Y1 - 2015/11
N2 - Background: Effective prevention is needed to combat the worldwide epidemic of type 2 diabetes. We investigated the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally shown during the 3-year Diabetes Prevention Program (DPP), and assessed whether these interventions reduced diabetes-associated microvascular complications. Methods: The DPP (1996-2001) was a randomised trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk of developing diabetes. All participants were offered lifestyle training at the end of the DPP. 2776 (88%) of the surviving DPP cohort were followed up in the DPP Outcomes Study (DPPOS, Sept 1, 2002, to Jan 2, 2014) and analysed by intention to treat on the basis of their original DPP assignment. During DPPOS, the original lifestyle intervention group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin. The primary outcomes were the development of diabetes and the prevalence of microvascular disease. For the assessment of microvascular disease, we used an aggregate microvascular outcome, composed of nephropathy, retinopathy, and neuropathy. Findings: During a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group (hazard ratio 0·73, 95% CI 0·65-0·83; p<0·0001) and by 18% in the metformin group (0·82, 0·72-0·93; p=0·001), compared with the placebo group, with declining between-group differences over time. At year 15, the cumulative incidences of diabetes were 55% in the lifestyle group, 56% in the metformin group, and 62% in the placebo group. The prevalences at the end of the study of the aggregate microvascular outcome were not significantly different between the treatment groups in the total cohort (placebo 12·4%, 95% CI 11·1-13·8; metformin 13·0%, 11·7-14·5; lifestyle intervention 11·3%, 10·1-12·7). However, in women (n=1887) the lifestyle intervention was associated with a lower prevalence (8·7%, 95% CI 7·4-10·2) than in the placebo (11·0%, 9·6-12·6) and metformin (11·2%, 9·7-12·9) groups, with reductions in the lifestyle intervention group of 21% (p=0·03) compared with placebo and 22% (p=0·02) compared with metformin. Compared with participants who developed diabetes, those who did not develop diabetes had a 28% lower prevalence of microvascular complications (relative risk 0·72, 95% CI 0·63-0·83; p<0·0001). Interpretation: Lifestyle intervention or metformin significantly reduced diabetes development over 15 years. There were no overall differences in the aggregate microvascular outcome between treatment groups; however, those who did not develop diabetes had a lower prevalence of microvascular complications than those who did develop diabetes. This result supports the importance of diabetes prevention. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.
AB - Background: Effective prevention is needed to combat the worldwide epidemic of type 2 diabetes. We investigated the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally shown during the 3-year Diabetes Prevention Program (DPP), and assessed whether these interventions reduced diabetes-associated microvascular complications. Methods: The DPP (1996-2001) was a randomised trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk of developing diabetes. All participants were offered lifestyle training at the end of the DPP. 2776 (88%) of the surviving DPP cohort were followed up in the DPP Outcomes Study (DPPOS, Sept 1, 2002, to Jan 2, 2014) and analysed by intention to treat on the basis of their original DPP assignment. During DPPOS, the original lifestyle intervention group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin. The primary outcomes were the development of diabetes and the prevalence of microvascular disease. For the assessment of microvascular disease, we used an aggregate microvascular outcome, composed of nephropathy, retinopathy, and neuropathy. Findings: During a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group (hazard ratio 0·73, 95% CI 0·65-0·83; p<0·0001) and by 18% in the metformin group (0·82, 0·72-0·93; p=0·001), compared with the placebo group, with declining between-group differences over time. At year 15, the cumulative incidences of diabetes were 55% in the lifestyle group, 56% in the metformin group, and 62% in the placebo group. The prevalences at the end of the study of the aggregate microvascular outcome were not significantly different between the treatment groups in the total cohort (placebo 12·4%, 95% CI 11·1-13·8; metformin 13·0%, 11·7-14·5; lifestyle intervention 11·3%, 10·1-12·7). However, in women (n=1887) the lifestyle intervention was associated with a lower prevalence (8·7%, 95% CI 7·4-10·2) than in the placebo (11·0%, 9·6-12·6) and metformin (11·2%, 9·7-12·9) groups, with reductions in the lifestyle intervention group of 21% (p=0·03) compared with placebo and 22% (p=0·02) compared with metformin. Compared with participants who developed diabetes, those who did not develop diabetes had a 28% lower prevalence of microvascular complications (relative risk 0·72, 95% CI 0·63-0·83; p<0·0001). Interpretation: Lifestyle intervention or metformin significantly reduced diabetes development over 15 years. There were no overall differences in the aggregate microvascular outcome between treatment groups; however, those who did not develop diabetes had a lower prevalence of microvascular complications than those who did develop diabetes. This result supports the importance of diabetes prevention. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.
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U2 - 10.1016/S2213-8587(15)00291-0
DO - 10.1016/S2213-8587(15)00291-0
M3 - Article
C2 - 26377054
AN - SCOPUS:84945463952
VL - 3
SP - 866
EP - 875
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
SN - 2213-8587
IS - 11
ER -
