Christine G Lee1, Brandy Heckman-Stoddard2, Dana Dabelea3, Kishore M Gadde4, David Ehrmann5, Leslie Ford2, Philip Prorok2, Edward J Boyko6, Xavier Pi-Sunyer7, Amisha Wallia8, William C Knowler9, Jill P Crandall10, Marinella Temprosa. 1. Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD dppmail@bsc.gwu.edu. 2. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD. 3. Department of Epidemiology and Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO. 4. Pennington Biomedical Research Center, Baton Rouge, LA. 5. University of Chicago, Chicago, IL. 6. Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle. 7. Columbia University Irving Medical Center, New York, New York. 8. Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. 9. Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ. 10. Division of Endocrinology and Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY.
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 originally 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, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.
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 originally 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, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.
Authors: T J Orchard; M Temprosa; E Barrett-Connor; S E Fowler; R B Goldberg; K J Mather; S M Marcovina; M Montez; R E Ratner; C D Saudek; H Sherif; K E Watson Journal: Diabet Med Date: 2013-01 Impact factor: 4.359
Authors: Edward W Gregg; Yiling J Cheng; Meera Srinivasan; Ji Lin; Linda S Geiss; Ann L Albright; Giuseppina Imperatore Journal: Lancet Date: 2018-05-18 Impact factor: 79.321
Authors: Richard R Rubin; Wilfred Y Fujimoto; David G Marrero; Tina Brenneman; Jeanne B Charleston; Sharon L Edelstein; Edwin B Fisher; Ruth Jordan; William C Knowler; Lynne C Lichterman; Melvin Prince; Patricia M Rowe Journal: Control Clin Trials Date: 2002-04
Authors: Rena R Wing; Rebecca H Neiberg; Judy L Bahnson; Jeanne M Clark; Mark A Espeland; James O Hill; Karen C Johnson; William C Knowler; KayLoni Olson; Helmut Steinburg; Xavier Pi-Sunyer; Thomas A Wadden; Holly Wyatt; Jeanne M Clark; Lee Swartz; Dawn Jiggetts; Jeanne Charleston; Lawrence Cheskin; Nisa M Maruthur; Scott J Pilla; Danielle Diggins; Mia Johnson; George A Bray; Frank L Greenway; Donna H Ryan; Catherine Champagne; Valerie Myers; Jeffrey Keller; Tiffany Stewart; Jennifer Arceneaux; Karen Boley; Greta Fry; Lisa Jones; Kim Landry; Melissa Lingle; Marisa Smith; Cora E Lewis; Sheikilya Thomas; Stephen Glasser; Gareth Dutton; Amy Dobelstein; Sara Hannum; Anne Hubbell; DeLavallade Lee; Phyllis Millhouse; L Christie Oden; Cathy Roche; Jackie Grant; Janet Turman; David M Nathan; Valerie Goldman; Linda Delahanty; Mary Larkin; Kristen Dalton; Roshni Singh; Melanie Ruazol; Medha N Munshi; Sharon D Jackson; Roeland J W Middelbeek; A Enrique Caballero; Anthony Rodriguez; George Blackburn; Christos Mantzoros; Ann McNamara; Holly Wyatt; James O Hill; Jeanne Anne Breen; Marsha Miller; Debbie Bochert; Suzette Bossart; Paulette Cohrs; Susan Green; April Hamilton; Eugene Leshchinskiy; Loretta Rome; John P Foreyt; Molly Gee; Henry Pownall; Ashok Balasubramanyam; Chu-Huang Chen; Peter Jones; Michele Burrington; Allyson Clark Gardner; Sharon Griggs; Michelle Hamilton; Veronica Holley; Sarah Lee; Sarah Lane Liscum; Susan Cantu-Lumbreras; Julieta Palencia; Jennifer Schmidt; Jayne Thomas; Carolyn White; Charlyne Wright; Monica Alvarez; Karen C Johnson; Beate Griffin; Mace Coday; Donna Valenski; Lisa Jones; Karen Johnson; Karen C Johnson; Helmut Steinburg; Robert W Jeffery; Tricia Skarphol; John P Bantle; J Bruce Redmon; Kerrin Brelje; Carolyne Campbell; Mary Ann Forseth; Soni Uccellini; Mary Susan Voeller; Blandine Laferrère; Xavier Pi-Sunyer; Jennifer Patricio; Jose Luchsinger; Priya Palta; Sarah Lyon; Kim Kelly; Thomas A Wadden; Barbara J Maschak-Carey; Robert I Berkowitz; Ariana Chao; Renee Davenport; Katherine Gruber; Sharon Leonard; Olivia Walsh; John M Jakicic; Jacqueline Wesche-Thobaben; Lin Ewing; Andrea Hergenroeder; Mary Korytkowski; Susan Copelli; Rebecca Danchenko; Diane Ives; Juliet Mancino; Lisa Martich; Meghan McGuire; Tracey Y Murray; Linda Semler; Kathy Williams; Rena R Wing; Caitlin Egan; Elissa Jelalian; Jeanne McCaffery; Kathryn Demos McDermott; Jessica Unick; Kirsten Annis; Jose DaCruz; Ariana Rafanelli; Helen P Hazuda; Juan Carlos Isaac; Prepedigna Hernandez; Steven E Kahn; Edward J Boyko; Elaine Tsai; Lorena Wright; Karen Atkinson; Ivy Morgan-Taggart; Jolanta Socha; Heidi Urquhart; William C Knowler; Paula Bolin; Harelda Anderson; Sara Michaels; Ruby Johnson; Patricia Poorthunder; Janelia Smiley; Anne L Peters; Siran Ghazarian; Elizabeth Beale; Edgar Ramirez; Gabriela Rodriguez; Valerie Ruelas; Sara Serafin-Dokhan; Martha Walker; Marina Perez; Mark A Espeland; Lynne E Wagenknecht; Judy L Bahnson; David Reboussin; Mike E Miller; Peter Brubaker; Nicholas Pajewski; Michael Bancks; Jingzhong Ding; Gagan Deep; Kathleen Hayden; Stephen R Rapp; Felicia Simpson; Haiying Chen; Bonnie C Sachs; Denise Houston; Shyh-Huei Chen; Andrea Anderson; Jerry M Barnes; Mary Barr; Tara D Beckner; Delilah R Cook; Carrie C Williams; Joni Evans; Katie Garcia; Sarah A Gaussoin; Carol Kittel; Lea Harvin; Marjorie Howard; James Lovato; Rebecca H Neiberg; June Pierce; Debbie Steinberg; Christopher Webb; Jennifer Walker; Michael P Walkup; Carolyn Watkins; Santica M Marcovina; Jessica Hurting; John J Albers; Vinod Gaur; Michael Nevitt; Ann Schwartz; John Shepherd; Michaela Rahorst; Lisa Palermo; Susan Ewing; Cynthia Hayashi; Jason Maeda Journal: Diabetes Care Date: 2022-04-14 Impact factor: 17.152
Authors: Rena R Wing; George A Bray; Maria Cassidy-Begay; Jeanne M Clark; Mace Coday; Caitlin Egan; Mary Evans; John P Foreyt; Stephen Glasser; Edward W Gregg; Helen P Hazuda; James O Hill; Edward S Horton; Juan Carlos Isaac; John M Jakicic; Robert W Jeffery; Karen C Johnson; Steven E Kahn; Stephen Kritchevsky; E Lewis; Nisa M Maruthur; Barbara J Maschak-Carey; David M Nathan; Jennifer Patricio; Anne Peters; Xavier Pi-Sunyer; David Reboussin; Donna H Ryan; Valerie Ruelas; Helmut Steinburg; Katie Toledo; Thomas A Wadden; Lynne E Wagenknecht; Jacqueline Wesche-Thobaben; Holly Wyatt; Susan Z Yanovski; Ping Zhang Journal: Diabetes Care Date: 2022-03-21 Impact factor: 17.152