John W. Apolzan, PhD; Elizabeth M. Venditti, PhD; Sharon L. Edelstein, ScM; William C. Knowler, MD, DrPH; Dana Dabelea, MD, PhD; Edward J. Boyko, MD; Xavier Pi-Sunyer, MD; Rita R. Kalyani, MD; Paul W. Franks, PhD; Preethi Srikanthan, MD; Kishore M. Gadde, MD; for the Diabetes Prevention Program Research Group *
Disclaimer: The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies.
Acknowledgment: The members of the DPP Research Group thank the participants in the DPP and the DPPOS for their commitment and dedication.
Grant Support: Research reported in this article was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under award number U01 DK048489. During the DPP and the DPPOS, the NIDDK provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study and the 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, the National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. 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 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. Bristol-Myers Squibb and Parke-Davis provided additional funding and material support during the DPP. Lipha (Merck-Santé) provided medication, and LifeScan donated materials during the DPP and the DPPOS. This research was also supported in part by the intramural research program of the NIDDK. LifeScan, Health o meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck and Company, Nike Sports Marketing, SlimFast Foods, and Quaker Oats donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group, and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center.
Disclosures: Dr. Pi-Sunyer reports personal fees from Novo Nordisk and Zafgen outside the submitted work. Dr. Franks reports grants from Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Sanofi Aventis, and Servier and personal fees from Zoe Global outside the submitted work. Dr. Gadde reports grants from AstraZeneca and BioKier and other support from AstraZeneca and the American Diabetes Association outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1605.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Data Sharing Statement: The authors have indicated that they will not be sharing data.
Corresponding Author: Kishore M. Gadde, MD, c/o DPPOS Coordinating Center, The George Washington University Biostatistics Center, 6110 Executive Boulevard, Suite 750, Rockville, MD 20852; e-mail, Kishore.firstname.lastname@example.org.
Current Author Addresses: Drs. Apolzan and Gadde: Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70810.
Dr. Venditti: Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O'Hara Street, Pittsburgh, PA 15213.
Ms. Edelstein: George Washington University Biostatistics Center, 6110 Executive Boulevard, Suite 750, Rockville, MD 20852.
Dr. Knowler: National Institute of Diabetes and Digestive and Kidney Diseases, 1550 East Indian School Road, Phoenix, AZ 85014.
Dr. Dabelea: Department of Epidemiology, Colorado School of Public Health, 13001 East 17th Avenue, Aurora, CO 80045.
Dr. Boyko: Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108.
Dr. Pi-Sunyer: Department of Medicine, Columbia University College of Physicians and Surgeons, 1150 St. Nicholas Avenue, Suite 121, New York, NY 10032.
Dr. Kalyani: School of Medicine, Johns Hopkins University, 1830 East Monument Street, Suite 333, Baltimore, MD 21287.
Dr. Franks: Lund University Diabetes Centre, Skåne University Hospital, Building 91, Jan Waldenströms gata 35, SE-205 02, Malmö, Sweden.
Dr. Srikanthan: Department of Medicine, University of California, Los Angeles, 330 South Garfield Avenue, Suite 308, Alhambra, CA 91801.
Author Contributions: Conception and design: J.W. Apolzan, E.M. Venditti, S.L. Edelstein, K.M. Gadde.
Analysis and interpretation of the data: J.W. Apolzan, E.M. Venditti, S.L. Edelstein, W.C. Knowler, D. Dabelea, K.M. Gadde.
Drafting of the article: J.W. Apolzan, E.M. Venditti, S.L. Edelstein, K.M. Gadde.
Critical revision of the article for important intellectual content: J.W. Apolzan, E.M. Venditti, S.L. Edelstein, W.C. Knowler, D. Dabelea, E.J. Boyko, X. Pi-Sunyer, R.R. Kalyani, P.W. Franks, P. Srikanthan, K.M. Gadde.
Final approval of the article: J.W. Apolzan, E.M. Venditti, S.L. Edelstein, W.C. Knowler, D. Dabelea, E.J. Boyko, X. Pi-Sunyer, R.R. Kalyani, P.W. Franks, P. Srikanthan, K.M. Gadde.
Provision of study materials or patients: E.M. Venditti, S.L. Edelstein, W.C. Knowler, X. Pi-Sunyer, K.M. Gadde.
Statistical expertise: S.L. Edelstein, W.C. Knowler.
Obtaining of funding: E.M. Venditti, S.L. Edelstein, W.C. Knowler, D. Dabelea, X. Pi-Sunyer, K.M. Gadde.
Administrative, technical, or logistic support: S.L. Edelstein, W.C. Knowler, K.M. Gadde.
Collection and assembly of data: S.L. Edelstein, W.C. Knowler, D. Dabelea, X. Pi-Sunyer, K.M. Gadde.
Identifying reliable predictors of long-term weight loss (LTWL) could lead to improved weight management.
To identify some predictors of LTWL.
The DPP (Diabetes Prevention Program) was a randomized controlled trial that compared weight loss with metformin, intensive lifestyle intervention (ILS), or placebo. Its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. (ClinicalTrials.gov: NCT00004992 and NCT00038727)
27 DPP and DPPOS clinics.
Of the 3234 randomly assigned participants, 1066 lost at least 5% of baseline weight in the first year and were followed for 15 years.
Treatment assignment, personal characteristics, and weight.
After 1 year, 289 (28.5%) participants in the metformin group, 640 (62.6%) in the ILS group, and 137 (13.4%) in the placebo group had lost at least 5% of their weight. After the masked treatment phase ended, the mean weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (95% CI, 5.2% to 7.2%) in the metformin group, 3.7% (CI, 3.1% to 4.4%) in the ILS group, and 2.8% (CI, 1.3% to 4.4%) in the placebo group. Independent predictors of LTWL included greater weight loss in the first year in all groups, older age and continued metformin use in the metformin group, older age and absence of either diabetes or a family history of diabetes in the ILS group, and higher fasting plasma glucose levels at baseline in the placebo group.
Post hoc analysis; examination of nonrandomized subsets of randomized groups after year 1.
Among persons with weight loss of at least 5% after 1 year, those originally randomly assigned to metformin had the greatest loss during years 6 to 15. Older age and the amount of weight initially lost were the most consistent predictors of LTWL maintenance.
National Institutes of Health.
DPP and DPPOS study design.
DPP = Diabetes Prevention Program; DPPOS = Diabetes Prevention Program Outcomes Study.
Appendix Table. Baseline Characteristics of Participants With <5% Versus ≥5% Weight Loss in the First Year
Study flow diagram.
Participants discontinued DPP and DPPOS visits for various reasons, including loss to follow-up, health and mobility issues, and death. DPP = Diabetes Prevention Program; DPPOS = Diabetes Prevention Program Outcomes Study; ILS = intensive lifestyle intervention; PCP = primary care provider.
Patterns of mean weight change over 15 years.
Error bars represent 95% CIs. Sample sizes were 289 at year one, 247 at year five, 236 at year ten, and 172 at year fifteen in the metformin group; 640 at year one, 540 at year five, 491 at year ten, and 373 at year fifteen in the intensive lifestyle intervention group; and 137 at year one, 110 at year five, 104 at year ten, and 92 at year fifteen in the placebo group. DPP = Diabetes Prevention Program; LTWL = long-term weight loss. Top. Observed weight loss over 15 y among all participants and those who lost <5% vs. ≥5% of their weight in the first year, by treatment group. Bottom. Observed percentages of participants with ≥5% weight loss each year in years 2 to 15 among those who lost ≥5% in the first year, by treatment group.
Predictors of long-term weight loss.
Results are from generalized estimating equation and multiple logistic regression models predicting ≥5% weight loss overall and at 5, 10, and 15 y. Odds ratios are displayed on a logarithmic scale. Error bars represent 95% CIs. Top. Metformin group. Older age at randomization (per 10 y), greater weight loss at year 1 (per 5%), and active use of study metformin increased odds of long-term weight loss. Middle. Intensive lifestyle intervention group. Older age at randomization (per 10 y) and greater weight loss at year 1 (per 5%) increased odds of long-term weight loss, whereas current diabetes status and family history of diabetes decreased odds. Bottom. Placebo group. Greater weight loss at year 1 (per 5%) and higher fasting glucose level (per 0.55 mmol/L [10 mg/dL]) were the only predictors of long-term weight loss.
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In this video, Kishore M. Gadde, MD, offers additional insight into the article, "Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study."
Apolzan JW, Venditti EM, Edelstein SL, Knowler WC, Dabelea D, Boyko EJ, et al. Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study. Ann Intern Med. [Epub ahead of print 23 April 2019]:. doi: 10.7326/M18-1605
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Published: Ann Intern Med. 2019.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism, Prevention/Screening.
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