Randomized Study of Metformin and Intensive Lifestyle Intervention on Cancer Incidence over 21 years of follow-up in the Diabetes Prevention Program

Authors

Brandy M. Heckman-Stoddard, National Cancer Institute, Rockville, MD, United States.
Jill P. Crandall, Albert Einstein College of Medicine, Bronx, NY, United States.
Sharon L. Edelstein, George Washington University, Rockville, MD, United States.
Philip C. Prorok, National Cancer Institute, Bethesda, United States.
Dana Dabelea, Colorado School of Public Health, Aurora, CO, United States.
Richard Hamman, Colorado School of Public Health, Aurora, CO, United States.
Helen P. Hazuda, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Edward Horton, Joslin Diabetes Center, United States.
Mary A. Hoskin, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, United States.
Marjorie Perloff, National Cancer Institute, Rockville, MD, United States.
Anna Bowers, George Washington University, Rockville, MD, United States.
William C. Knowler, George Washington University, Rockville, MD, United States.
Leslie G. Ford, National Cancer Institute, rockville, MD, United States.
Marinella Temprosa, George Washington University, Rockville, MD, United States.

Document Type

Journal Article

Publication Date

4-17-2025

Journal

Cancer prevention research (Philadelphia, Pa.)

DOI

10.1158/1940-6207.CAPR-23-0461

Abstract

Meta-analyses have reported a decrease in overall cancer incidence of approximately 10-40% with metformin use among individuals with diabetes. Lifestyle change could potentially reduce cancer incidence. The objective was to determine whether metformin or intensive lifestyle intervention (ILS) reduces the risk of cancer among adults at high risk of diabetes. The Diabetes Prevention Program (DPP, 1996-2001) randomized 3234 participants to ILS, metformin (850 mg twice daily), or blinded placebo. During follow-up through the DPP Outcomes Study (DPPOS), all participants were offered a modified lifestyle intervention, and metformin continued open-label metformin group. Participants reported cancer cases annually. Medical records were adjudicated for all reported events. The primary endpoint was total cancer incidence, comparing metformin versus placebo, with ILS versus placebo as a secondary objective. After a median follow-up of 21 years, 546 participants (173 metformin, 182 ILS, and 191 placebo) were diagnosed with a first incident cancer. Incidence rates of cancer were 9.8, 10.5, and 10.8 per 1,000 person-years in metformin, ILS, and placebo, respectively, with a hazard ratio (HR) of 0.90 (95%CI = 0.73 to 1.10) for metformin compared to placebo and 0.96 (95%CI = 0.79 to 1.18) for ILS compared to placebo. There were no differences between any treatment groups for obesity-related cancer or in sex-specific analyses. Neither assignment to metformin nor ILS reduced cancer incidence among adults at high risk of diabetes. These results may be impacted by increased non-study metformin usage over time due to the development of diabetes and reduced intensity of ILS intervention over time.

APA Citation

Heckman-Stoddard, Brandy M.; Crandall, Jill P.; Edelstein, Sharon L.; Prorok, Philip C.; Dabelea, Dana; Hamman, Richard; Hazuda, Helen P.; Horton, Edward; Hoskin, Mary A.; Perloff, Marjorie; Bowers, Anna; Knowler, William C.; Ford, Leslie G.; and Temprosa, Marinella, "Randomized Study of Metformin and Intensive Lifestyle Intervention on Cancer Incidence over 21 years of follow-up in the Diabetes Prevention Program" (2025). GW Authored Works. Paper 7035.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7035

Department

Emergency Medicine