학술논문
Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study
Document Type
article
Author
Lee, Christine G; Heckman-Stoddard, Brandy; Dabelea, Dana; Gadde, Kishore M; Ehrmann, David; Ford, Leslie; Prorok, Philip; Boyko, Edward J; Pi-Sunyer, Xavier; Wallia, Amisha; Knowler, William C; Crandall, Jill P; Temprosa, Marinella; Group:, Diabetes Prevention Program Research; Bray, George A; Culbert, Iris W; Arceneaux, Jennifer; Chatellier, Annie; Dragg, Amber; Champagne, Catherine M; Duncan, Crystal; Eberhardt, Barbara; Greenway, Frank; Guillory, Fonda G; Herbert, April A; Jeffirs, Michael L; Kennedy, Betty M; Levy, Erma; Lockett, Monica; Lovejoy, Jennifer C; Morris, Laura H; Melancon, Lee E; Ryan, Donna H; Sanford, Deborah A; Smith, Kenneth G; Smith, Lisa L; St. Amant, Julia A; Tulley, Richard T; Vicknair, Paula C; Williamson, Donald; Zachwieja, Jeffery J; Polonsky, Kenneth S; Tobian, Janet; Ehrmann, David A; Matulik, Margaret J; Temple, Karla A; Clark, Bart; Czech, Kirsten; DeSandre, Catherine; Dotson, Brittnie; Hilbrich, Ruthanne; McNabb, Wylie; Semenske, Ann R; Caro, Jose F; Furlong, Kevin; Goldstein, Barry J; Watson, Pamela G; Smith, Kellie A; Mendoza, Jewel; Simmons, Marsha; Wildman, Wendi; Liberoni, Renee; Spandorfer, John; Pepe, Constance; Donahue, Richard P; Goldberg, Ronald B; Prineas, Ronald; Calles, Jeanette; Giannella, Anna; Rowe, Patricia; Sanguily, Juliet; Cassanova-Romero, Paul; Castillo-Florez, Sumaya; Florez, Hermes J; Garg, Rajesh; Kirby, Lascelles; Lara, Olga; Larreal, Carmen; McLymont, Valerie; Mendez, Jadell; Perry, Arlette; Saab, Patrice; Veciana, Bertha; Haffner, Steven M; Hazuda, Helen P; Montez, Maria G; Hattaway, Kathy; Isaac, Juan; Lorenzo, Carlos; Martinez, Arlene; Salazar, Monica; Walker, Tatiana; Hamman, Richard F; Nash, Patricia V; Steinke, Sheila C; Testaverde, Lisa; Truong, Jennifer; Anderson, Denise R
Source
Diabetes Care. 44(12)
Subject
Language
Abstract
ObjectiveTo 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 methodsFrom 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.ResultsOver 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.ConclusionsCancer 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.