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Cited by 29Diabetes, Cardiovascular Risks, and LipoproteinsDiabetes Treatment and ManagementDiabetes Management and Research

The Diabetes Prevention Program and Its Outcomes Study: NIDDK’s Journey Into the Prevention of Type 2 Diabetes and Its Public Health Impact

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Crandall, Jill P., Dabelea, Dana, Knowler, William C., Nathan, David M., Temprosa, Marinella, DPP Research Group, Bray, George A., Gadde, Kishore M. +669 more·2025·Diabetes Care
DOI 10.2337/dc25-0014PMC PMC12178622
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Abstract

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS reduced diabetes risk by 58% and metformin by 31%, leading to study termination ahead of schedule due to demonstrated efficacy of both interventions. In 2002, an extension of the DPP study, the Diabetes Prevention Program Outcomes Study (DPPOS), was initiated for examination of the longer-term course and consequences of diabetes prevention. Over 21 years of median total follow-up, in comparison with the placebo group, cumulative diabetes incidence was reduced by 24% and 17% in the original ILS and metformin groups, respectively, with median increases in diabetes-free survival of 3.5 and 2.5 years/person. During long-term follow-up, there were no significant effects of the original DPP interventions on microvascular or cardiovascular outcomes. However, compared with prevalence of microvascular outcomes among participants who progressed to diabetes, prevalence among those who did not progress was significantly lower. Longer-term follow-up of the cohort continues with examination of relationships between diabetes and prediabetes and an expanded array of diabetes- and aging-related morbidities.

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  • The most successful weight-loss trials to date-including the STEP program for semaglutide and the SURMOUNT program for tirzepatide-have incorporated intensive lifestyle interventions as a core component of the trial protocol, modeled on the structured behavioral curricula pioneered by the Diabetes Prevention Program.

    “The most successful weight-loss trials to date—including the STEP program for semaglutide [9] and the SURMOUNT program for tirzepatide [13]—have incorporated intensive lifestyle interventions as a core component of the trial protocol, modeled on the structured behavioral curricula pioneered by the Diabetes Prevention Program (DPP) [76,77].”

    From Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review (2026) · cites this paper as [77]

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  • Pivotal randomized trials of GLP-1 RAs for obesity (STEP, SURMOUNT, SCALE) all incorporated intensive lifestyle interventions modeled on Diabetes Prevention Program-style curricula, and the magnitude of weight loss in the control arms confirms that structured lifestyle support produces clinically meaningful effects in this population even without GLP-1 RA therapy.

    “pivotal randomized trials of GLP-1 RAs for obesity (STEP, SURMOUNT, SCALE) all incorporated intensive lifestyle interventions modeled on Diabetes Prevention Program-style curricula, and the magnitude of weight loss in the control arms of these trials confirms that structured lifestyle support produces clinically meaningful effects in this population even without GLP-1 RA therapy [9,13,76,77].”

    From Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review (2026) · cites this paper as [77]

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References 67 · Cited by 29

Research works printed but not linked: 1

  1. [31]Knowler W, Doherty L, Edelstein S, Effects of lifestyle and metformin interventions on diabetes incidence over 21 median years follow-up of the US Diabetes Prevention Program randomized clinical trial: assessment of heterogeneity. Lancet Diabetes Endocrinol. In press PMC12414453 40311647

Authors
Crandall, J. P., Dabelea, D., Knowler, W. C., Nathan, D. M., Temprosa, M., DPP Research Group, Bray, G. A., Gadde, K. M., Culbert, I. W., Arceneaux, J., Chatellier, A., Dragg, A., Champagne, C. M., Duncan, C., Eberhardt, B., Greenway, F., Guillory, F. G., Herbert, A. A., Jeffirs, M. L., Kennedy, B. M., Levy, E., Lockett, M., Lovejoy, J. C., Morris, L. H., Melancon, L. E., Ryan, D. H., Sanford, D. A., Smith, K. G., Smith, L. L., St.Amant, J. A., Tulley, R. T., Vicknair, P. C., Williamson, D., Zachwieja, J. J., Polonsky, K. S., Tobian, J., Ehrmann, D. A., Matulik, M. J., Temple, K. A., Clark, B., Czech, K., DeSandre, C., Dotson, B., Hilbrich, R., McNabb, W., Semenske, A. R., Thomas, C. C., Caro, J. F., Furlong, K., Goldstein, B. J., Watson, P. G., Smith, K. A., Mendoza, J., Simmons, M., Wildman, W., Liberoni, R., Spandorfer, J., Pepe, C., Donahue, R. P., Goldberg, R. B., Prineas, R., Calles, J., Giannella, A., Rowe, P., Sanguily, J., Cassanova-Romero, P., Castillo-Florez, S., Florez, H. J., Garg, R., Kirby, L., Lara, O., Larreal, C., McLymont, V., Mendez, J., Perry, A., Saab, P., Veciana, B., Haffner, S. M., Hazuda, H. P., Montez, M. G., Hattaway, K., Isaac, J., Lorenzo, C., Martinez, A., Salazar, M., Walker, T., Dabelea, D., Hamman, R. F., Nash, P. V., Steinke, S. C., Testaverde, L., Truong, J., Anderson, D. R., Ballonoff, L. B., Bouffard, A., Bucca, B., Calonge, B. N., Delve, L., Farago, M., Hill, J. O., Hoyer, S. R., Jenkins, T., Jortberg, B. T., Lenz, D., Miller, M., Nilan, T., Perreault, L., Price, D. W., Regensteiner, J. G., Schroeder, E. B., Seagle, H., Smith, C. M., VanDorsten, B., Horton, E. S., Munshi, M., Lawton, K. E., Jackson, S. D., Poirier, C. S., Swift, K., Arky, R. A., Bryant, M., Burke, J. P., Caballero, E., Callaphan, K. M., Fargnoli, B., Franklin, T., Ganda, O. P., Guidi, A., Guido, M., Jacobsen, A. M., Kula, L. M., Kocal, M., Lambert, L., Lawton, K. E., Ledbury, S., Malloy, M. A., Middelbeek, R. J. W., Nicosia, M., Oldmixon, C. 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J., Lukin, J., Kloiber, S., Longchamp, N., Martinez, H., Pompi, D., Scheindlin, J., Violino, E., Walker, E. A., Wylie-Rosett, J., Zimmerman, E., Zonszein, J., Orchard, T., Venditti, E., Wing, R. R., Jeffries, S., Koenning, G., Kramer, M. K., Smith, M., Barr, S., Benchoff, C., Boraz, M., Clifford, L., Culyba, R., Frazier, M., Gilligan, R., Guimond, S., Harrier, S., Harris, L., Kriska, A., Manjoo, Q., Mullen, M., Noel, A., Otto, A., Pettigrew, J., Rockette-Wagner, B., Rubinstein, D., Semler, L., Smith, C. F., Weinzierl, V., Williams, K. V., Wilson, T., Gillis, B., Mau, M. K., Baker-Ladao, N. K., Melish, J. S., Arakaki, R. F., Latimer, R. W., Isonaga, M. K., Beddow, R., Bermudez, N. E., Dias, L., Inouye, J., Mikami, K., Mohideen, P., Odom, S. K., Perry, R. U., Yamamoto, R. E., Knowler, W. C., Hanson, R. L., Anderson, H., Cooeyate, N., Dodge, C., Hoskin, M. A., Percy, C. A., Enote, A., Natewa, C., Acton, K. J., Andre, V. L., Barber, R., Begay, S., Bennett, P. H., Benson, M. B., Bird, E. 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Z., Hu, J., Hensley, S., Keasler, L., Taylor, T., Blodi, B., Danis, R., Davis, M., Hubbard, L., Endres, R., Elsas, D., Johnson, S., Myers, D., Barrett, N., Baumhauer, H., Benz, W., Cohn, H., Corkery, E., Dohm, K., Domalpally, A., Gama, V., Goulding, A., Ewen, A., Hurtenbach, C., Lawrence, D., McDaniel, K., Pak, J., Reimers, J., Shaw, R., Swift, M., Vargo, P., Watson, S., Luchsinger, J. A., Manly, J., Mayer-Davis, E., Moran, R. R., Ganiats, T., David, K., Sarkin, A. J., Groessl, E., Katzir, N., Chong, H., Herman, W. H., Brändle, M., Brown, M. B., Altshuler, D., Billings, L. K., Chen, L., Harden, M., Pollin, T. I., Shuldiner, A. R., Franks, P. W., & Hivert, M.-F.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2025-04-24
Volume
48
Issue
7
Pages
1101-1111
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc25-0014
PMC
PMC12178622
OpenAlex
W4409781833
Cited by
29
References
67
Citations by year
2026: 20 · 2025: 9
FWCI
3.91
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/journals/pages/license (vor)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK048339, U01 DK048349, U01 DK048375, U01 DK048377, U01 DK048380, U01 DK048381, U01 DK048387, U01 DK048397, U01 DK048400, U01 DK048404, U01 DK048406, U01 DK048407, U01 DK048411, U01 DK048412, U01 DK048413, U01 DK048434, U01 DK048437, U01 DK048443, U01 DK048468, U01 DK048485, U01 DK048489, U01 DK048514)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
Diabetes Prevention Program, Diabetes Prevention Program Outcomes Study, type 2 diabetes prevention, prediabetes, intensive lifestyle intervention, metformin, National Institute of Diabetes and Digestive and Kidney Diseases, diabetes incidence, microvascular complications, cardiovascular outcomes, adiposity, physical activity
MeSH terms
Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Life Style, Male, Metformin, Prediabetic State, Public Health, United States, Randomized Controlled Trials as Topic, National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)

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