Long-term Effects of Metformin on Diabetes Prevention: Identification of Subgroups That Benefited Most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study

• DOI: 10.2337/dc18-1970
• Publication Date: 2019-03-15T19:11:46Z
• Authors: David M. Nathan; William C. Knowler; Sharon Edelstein; Jill P. Crandall; Dana Dabelea; Ronald B. Goldberg; Steven E. Kahn; Kieren J. Mather; Gilda Trandafirescu; Elizabeth A. Walker; Marinella Temprosa; George A. Bray; Kishore Gadde; Annie Chatellier; Jennifer Arceneaux; Amber Dragg; Crystal Duncan; Frank L. Greenway; Daniel Hsia; Erma Levy; Monica Lockett; Donna H. Ryan; David Ehrmann; Margaret J. Matulik; Kirsten Czech; Catherine DeSandre; Barry J. Goldstein; Kevin Furlong; Kellie A. Smith; Wendi Wildman; Constance Pepe; Jeanette Calles; Juliet Ojito; Sumaya Castillo-F...; Anna Giannella; Olga Lara; Beth Veciana; Steven M. Haffner; Helen P. Hazuda; Maria G. Montez; Kathy Hattaway; Carlos Lorenzo; Arlene Martinez; Tatiana Walker; Richard F. Hamman; Lisa Testaverde; Denise Anderson; Alexis Bouffard; Tonya Jenkins; Dione Lenz; Leigh Perreault; David W. Price; Sheila C. Steinke; Edward S. Horton; Catherine S. Poirier; Kati Swift; Enrique Caballero; Barbara Fargnoli; Ashley Guidi; Mathew Guido; Sharon D. Jackson; Lori Lambert; Kathleen E. Lawton; Sarah Ledbury; Jessica Sansoucy; Jeanne Spellman; Brenda K. Montgomery; Wilfred Fujimoto; Robert H. Knopp; Edward W. Lipkin; Ivy Morgan-Taggart; Anne Murillo; Lonnese Taylor; April Thomas; Elaine C. Tsai; Dace Trence; Abbas E. Kitabchi; Samuel Dagogo-Jack; Mary E. Murphy; Laura Taylor; Jennifer Dolgoff; Debra Clark; Uzoma Ibebuogu; Helen Lambeth; Harriet Ricks; Lily M.K. Rutledge; Judith E. Soberman; Mark E. Molitch; Boyd E. Metzger; Mariana K. Johnson; Mimi M. Giles; Diane Larsen; Samsam C. Pen; Mary Larkin; Charles McKitrick; Heather Turgeon; Ellen Anderson; Laurie Bissett; Kristy Bondi; Enrico Cagliero; Kali D’Anna; Linda Delahanty; Jose C. Florez; Valerie Goldman; Peter Lou; Alexandra Poulos; Elyse Raymond; Christine Stevens; Beverly Tsent; Elizabeth Barrett...; Mary Lou Carrion-...; Lauren N. Claravall; Jonalle M. Dowden; Javiva Horne; Diana Leos; Sundar Mudaliar; Jean Smith; Simona Szerdi Jan...; Karen Vejvoda; F. Xavier Pi-Sunyer; Jane E. Lee; Sandra T. Foo; Susan Hagamen; David G. Marrero; Susie M. Kelly; Paula Putenney; Marcia A. Jackson; Gina McAtee; Ronald T. Ackermann; Carolyn M. Cantrell; Edwin S. Fineberg; Angela Hadden; Mario S. Kirkman; Erin O’Kelly Phil...; Paris J. Roach; Robert E. Ratner; Vanita Aroda; Sue Shapiro; Catherine Bavido-...; Peggy Gibbs; Gabriel Uwaifo; Renee Wiggins; Mohammed F. Saad; Karol Watson; Medhat Botrous; Sujata Jinagouda; Maria Budget; Claudia Conzues; Perpetua Magpuri; Kathy Ngo; Kathy Xapthalamous; Neil H. White; Angela L. Brown; Samia Das; Prajakta Khare-Ra...; Tamara Stich; Ana Santiago; Cormarie Wernimont; Christopher D. Sa...; Sherita Hill Golden; Tracy Whittington; Frederick L. Bran...; Jeanne M. Clark; Alicia Greene; Dawn Jiggetts; Henry Mosley; John Reusing; Richard R. Rubin; Shawne Stephens; Evonne Utsey; David S. Shade; Karwyn S. Adams; Claire Hemphill; Penny Hyde; Janene L. Canady; Kathleen Colleran; Ysela Gonzeles; Doris A. Hernande...; Carolyn King; Jill Crandall; Janet O. Brown; Elsie Adorno; Helena Duffy; Angela Goldstein; Jennifer Lukin; Helen Martinez; Dorothy Pompi; Harry Shamoon; Jonathan Scheindlin; Judith Wylie-Rosett; Trevor Orchard; Andrea Kriska; Susan Jeffries; M. Kaye Kramer; Marie Smith; Catherine Benchoff; Stephanie Guimond; Jessica Pettigrew; Debra Rubinstein; Linda Semler; Elizabeth Venditti; Valarie Weinzierl; Richard F. Arakaki; Narleen K. Baker-...; Mae K. Isonaga; Nina E. Bermudez; Marjorie K. Mau; John S. Melish; Robin E. Yamamoto; Norman Cooeyate; Alvera Enote; Mary A. Hoskin; Camille Natewa; Carol A. Percy; Kelly J. Acton; Vickie L. Andre; Roz Barber; Shandiin Begay; Brian C. Bucca; Sherron Cook; Jeff Curtis; Charlotte Dodge; Matthew S. Doughty; Jason Kurland; Justin Glass; Martia Glass; Roberta L. Hanson; Louise E. Ingraham; Kathleen M. Kobus; Jonathan Krakoff; Catherine Manus; Cherie McCabe; Sara Michaels; Tina Morgan; Julie A. Nelson; Christopher Pirom...; Robert J. Roy; Sandra Sangster; Miranda Smart; Darryl P. Tonemah; Rachel Williams; Charlton Wilson; Sarah Fowler; Michael Larsen; Tina Brenneman; Hanna Sherif; Solome Abebe; Julie Bamdad; Melanie Barkalow; Joel Bethepu; Tsedenia Bezebeh; Nicole Butler; Jackie Callaghan; Caitlin E. Carter; Costas Christophi; Gregory M. Dwyer; Mary Foulkes; Yuping Gao; Robert Gooding; Adrienne Gottlieb; Nisha Grover; Heather Hoffman; Ashley N. Hogan; Kathleen Jablonski; Richard Katz; Preethy Kolinjivadi; John M. Lachin; Yong Ma; Qing Pan; Susan Reamer; Alla Sapozhnikova; Elizabeth M. Vend...; Andrea M. Kriska; Linda Semler; Valerie Weinzierl; Santica Marcovina; Greg Strylewicz; John Albers; Judith Fradkin; Stanford Garfield; Christine Lee; Edward Gregg; Ping Zhang; William H. Herman; Michael Brändle; Morton B. Brown
• Keywords: Primary Prevention

We examined the effects of metformin on diabetes prevention and subgroups that benefited most over 15 years in Diabetes Prevention Program (DPP) its follow-up, Outcomes Study (DPPOS).During DPP (1996-2001), adults at high risk developing were randomly assigned to masked placebo (n = 1,082) or 850 mg twice daily 1,073). Participants originally continued receive metformin, unmasked, DPPOS (2002-present). Ascertainment development was based fasting 2-h glucose levels after an oral tolerance test HbA1c. Reduction incidence with compared by hazard ratio (HR) rate differences (RDs).During postrandomization reduced (by HR) 17% 36% HbA1c levels, respectively. Metformin's effect glucose-defined greater for women a history prior gestational mellitus (GDM) (HR 0.59, RD -4.57 cases/100 person-years) parous without GDM 0.94, -0.38 person-years [interaction P 0.03 HR, 0.01 RD]). Metformin also had effects, HR RD, higher baseline levels. With HbA1c, more effective subjects -1.03 <6.0% (42 mmol/mol) -3.88 6.0-6.4% (P 0.0001).Metformin reduces years. The subsets benefitted include GDM.