Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study

John W Apolzan, Elizabeth M Venditti, Sharon L Edelstein, William C Knowler, Dana Dabelea, Edward J Boyko, Xavier Pi-Sunyer, Rita R Kalyani, Paul W Franks, Preethi Srikanthan, Kishore M Gadde, Diabetes Prevention Program Research Group, George A Bray, Kishore Gadde, Annie Chatellier, Jennifer Arceneaux, Amber Dragg, Crystal Duncan, Frank L Greenway, 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, Ronald B Goldberg, Jeanette Calles, Juliet Ojito, Sumaya Castillo-Florez, Hermes J Florez, 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, Dana Dabelea, 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, Steven E Kahn, 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, David M Nathan, 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 Tseng, Elizabeth Barrett-Connor, Mary Lou Carrion-Petersen, Lauren N Claravall, Jonalle M Dowden, Javiva Horne, Diana Leos, Sundar Mudaliar, Jean Smith, Simona Szerdi Janisch, Karen Vejvoda, F. Xavier Pi-Sunyer, Jane E Lee, Sandra T Foo, Susan Hagamen, David G Marrero, Kieren J Mather, 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 Phillips, Paris J Roach, Robert E Ratner, Vanita Aroda, Sue Shapiro, Catherine Bavido-Arrage, 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-Ranade, Tamara Stich, Ana Santiago, Cormarie Wernimont, Christopher D Saudek, Sherita Hill Golden, Tracy Whittington, Frederick L Brancati, Jeanne M Clark, Alicia Greene, Dawn Jiggetts, John Mosley, Richard R Rubin, Shawne Stephens, Evonne Utsey, David S Schade, Karwyn S Adams, Claire Hemphill, Penny Hyde, Janene L Canady, Kathleen Colleran, Ysela Gonzales, Doris A Hernandez-McGinnis, Carolyn King, Jill Crandall, Janet O Brown, Gilda Trandafirescu, Elsie Adorno, Helena Duffy, Angela Goldstein, Jennifer Lukin, Helen Martinez, Dorothy Pompi, Harry Shamoon, Jonathan Scheindlin, Elizabeth A Walker, 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-Ladao, Mae K Isonaga, Nina E Bermudez, Marjorie K Mau, John S Melish, Robin E Yamamoto, William C Knowler, 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, Robert L Hanson, Louise E Ingraham, Kathleen M Kobus, Jonathan Krakoff, Catherine Manus, Cherie McCabe, Sara Michaels, Tina Morgan, Julie A Nelson, Christopher Piromalli, Robert J Roy, Sandra Sangster, Miranda Smart, Darryl P Tonemah, Rachel Williams, Charlton Wilson, Sarah Fowler, Marinella Temprosa, Michael Larsen, Tina Brenneman, Hanna Sherif, Sharon L Edelstein, Solome Abebe, Julie Bamdad, Melanie Barkalow, Joel Bethepu, Tsedenia Bezabeh, 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, Andrea M Kriska, Linda Semler, Valerie Weinzierl, Santica Marcovina, Greg Strylewicz, John Albers, Judith Fradkin, Sanford Garfield, Christine Lee, Edward Gregg, Ping Zhang, William H Herman, Michael Brändle, Morton B Brown, John W Apolzan, Elizabeth M Venditti, Sharon L Edelstein, William C Knowler, Dana Dabelea, Edward J Boyko, Xavier Pi-Sunyer, Rita R Kalyani, Paul W Franks, Preethi Srikanthan, Kishore M Gadde, Diabetes Prevention Program Research Group, George A Bray, Kishore Gadde, Annie Chatellier, Jennifer Arceneaux, Amber Dragg, Crystal Duncan, Frank L Greenway, 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, Ronald B Goldberg, Jeanette Calles, Juliet Ojito, Sumaya Castillo-Florez, Hermes J Florez, 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, Dana Dabelea, 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, Steven E Kahn, 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, David M Nathan, 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 Tseng, Elizabeth Barrett-Connor, Mary Lou Carrion-Petersen, Lauren N Claravall, Jonalle M Dowden, Javiva Horne, Diana Leos, Sundar Mudaliar, Jean Smith, Simona Szerdi Janisch, Karen Vejvoda, F. Xavier Pi-Sunyer, Jane E Lee, Sandra T Foo, Susan Hagamen, David G Marrero, Kieren J Mather, 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 Phillips, Paris J Roach, Robert E Ratner, Vanita Aroda, Sue Shapiro, Catherine Bavido-Arrage, 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-Ranade, Tamara Stich, Ana Santiago, Cormarie Wernimont, Christopher D Saudek, Sherita Hill Golden, Tracy Whittington, Frederick L Brancati, Jeanne M Clark, Alicia Greene, Dawn Jiggetts, John Mosley, Richard R Rubin, Shawne Stephens, Evonne Utsey, David S Schade, Karwyn S Adams, Claire Hemphill, Penny Hyde, Janene L Canady, Kathleen Colleran, Ysela Gonzales, Doris A Hernandez-McGinnis, Carolyn King, Jill Crandall, Janet O Brown, Gilda Trandafirescu, Elsie Adorno, Helena Duffy, Angela Goldstein, Jennifer Lukin, Helen Martinez, Dorothy Pompi, Harry Shamoon, Jonathan Scheindlin, Elizabeth A Walker, 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-Ladao, Mae K Isonaga, Nina E Bermudez, Marjorie K Mau, John S Melish, Robin E Yamamoto, William C Knowler, 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, Robert L Hanson, Louise E Ingraham, Kathleen M Kobus, Jonathan Krakoff, Catherine Manus, Cherie McCabe, Sara Michaels, Tina Morgan, Julie A Nelson, Christopher Piromalli, Robert J Roy, Sandra Sangster, Miranda Smart, Darryl P Tonemah, Rachel Williams, Charlton Wilson, Sarah Fowler, Marinella Temprosa, Michael Larsen, Tina Brenneman, Hanna Sherif, Sharon L Edelstein, Solome Abebe, Julie Bamdad, Melanie Barkalow, Joel Bethepu, Tsedenia Bezabeh, 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, Andrea M Kriska, Linda Semler, Valerie Weinzierl, Santica Marcovina, Greg Strylewicz, John Albers, Judith Fradkin, Sanford Garfield, Christine Lee, Edward Gregg, Ping Zhang, William H Herman, Michael Brändle, Morton B Brown

Abstract

Background: Identifying reliable predictors of long-term weight loss (LTWL) could lead to improved weight management.

Objective: To identify some predictors of LTWL.

Design: The DPP (Diabetes Prevention Program) was a randomized controlled trial that compared weight loss with metformin, intensive lifestyle intervention (ILS), or placebo. Its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. (ClinicalTrials.gov: NCT00004992 and NCT00038727).

Setting: 27 DPP and DPPOS clinics.

Participants: Of the 3234 randomly assigned participants, 1066 lost at least 5% of baseline weight in the first year and were followed for 15 years.

Measurements: Treatment assignment, personal characteristics, and weight.

Results: After 1 year, 289 (28.5%) participants in the metformin group, 640 (62.6%) in the ILS group, and 137 (13.4%) in the placebo group had lost at least 5% of their weight. After the masked treatment phase ended, the mean weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (95% CI, 5.2% to 7.2%) in the metformin group, 3.7% (CI, 3.1% to 4.4%) in the ILS group, and 2.8% (CI, 1.3% to 4.4%) in the placebo group. Independent predictors of LTWL included greater weight loss in the first year in all groups, older age and continued metformin use in the metformin group, older age and absence of either diabetes or a family history of diabetes in the ILS group, and higher fasting plasma glucose levels at baseline in the placebo group.

Limitation: Post hoc analysis; examination of nonrandomized subsets of randomized groups after year 1.

Conclusion: Among persons with weight loss of at least 5% after 1 year, those originally randomly assigned to metformin had the greatest loss during years 6 to 15. Older age and the amount of weight initially lost were the most consistent predictors of LTWL maintenance.

Primary funding source: National Institutes of Health.

Figures

Figure 1.. Patterns of weight changes over…
Figure 1.. Patterns of weight changes over 15 years.
(A) Shown is the observed percent weight loss over 15 years for all participants by treatment group and for the subsets of participants who achieved <5% or ≥5% weight loss at Year 1. Data shown are Mean ± 95% Confidence Intervals (CI). (B) Shown are the observed percentages of participants by treatment group achieving ≥5% weight loss yearly during Years 2–15 among participants who achieved ≥5% weight loss at Year 1. Data shown are Mean ± 95% CI. Sample sizes: Metformin Year 1: 289, Year 5: 247, Year 10: 236. Year 15: 172. Intensive Lifestyle: Year 1: 640, Year 5: 540, Year 10: 491, Year 15: 373. Placebo: Year 1: 137, Year 5: 110, Year 10: 104, Year 15: 92.
Figure 2.. Predictors of long-term weight loss.
Figure 2.. Predictors of long-term weight loss.
Metformin (A), Intensive Lifestyle (ILS) (B), and Placebo (C). GEE and Multiple Logistic Regression Models Predicting ≥ 5% Weight Loss overall and at 5, 10, and 15 years (Odds Ratios & 95% CI). Odds ratios are displayed on a log scale. With Metformin (A), older age at randomization (per 10 years), greater % weight loss at Year 1 (per 5%), and active use of study metformin increased odds of long-term weight loss (LTWL). With ILS (B), older age at randomization (per 10 years) and greater % weight loss at Year 1 (per 5%) increased odds of LTWL, and current diabetes status, and a family history of diabetes decreased the odds of LTWL. With Placebo (C), greater % weight loss at Year 1 (per 5%) and higher fasting glucose (per 0.55 mmol/L [10 mg/dl]) were the only predictors of LTWL. ILS = intensive lifestyle; LTWL = long-term weight loss

Source: PubMed

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