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3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

2017; Elsevier BV; Volume: 389; Issue: 10077 Linguagem: Inglês

10.1016/s0140-6736(17)30069-7

1474-547X

Carel W. le Roux, Arne Astrup, Ken Fujioka, Frank L. Greenway, David Lau, Luc Van Gaal, Rafael Violante Ortíz, John Wilding, Trine Vang Skjøth, Linda Shapiro Manning, F. Xavier Pi‐Sunyer, A. Hamann, Alain Barakat, Matthias Blüher, Thomas Linn, Andrea Mölle, Alexander Segner, Petra Stübler, Regina Tosch-Sisting, Furio Pacini, Ferruccio Santini, Giulio Marchesini, Carlo Maria Rotella, Cecilia Invitti, Roberto Vettor, Silvio Buscemi, Pedro Mezquita Raya, Felipe Casanueva Freijoo, Ramón Gomis de Barbará, Raffaele Carraro, Enrique Romero Bobillo, Carmen de la Cuesta, Csaba Farsang, Albert Császár, Barbara Zahorska‐Markiewicz, Danuta Pupek-Musialik, Edward Franek, Lucyna Ostrowska, Magdalena Olszanecka‐Glinianowicz, Nebojša Lalić, Dragan Micić, Bernhard Ludvik, Bernhard Paulweber, Rudolf Prager, André Scheen, Luc Van Gaal, Arne Astrup, Kjeld Hermansen, Sten Madsbad, Aila Rissanen, Sakari Nieminen, Markku J. Savolainen, Michel Krempf, Monique Romon, M. Laville, Michel Marre, R Mira, Francis Finucane, Aletha Veenendaal, Frank van Berkum, Solrun Johannsson-Vidarsdóttir, Vivienne Van de Walle, Eelco W. Meesters, Jøran Hjelmesæth, Tor Ole Klemsdal, Bård Kulseng, Birgit Bach-Kliegel, Kurt Laederach, Lukas Villiger, Alain Golay, Stefan Bilz, Thozhukat Sathyapalan, Stephen C. Bain, Sudhesh Kumar, Carel Wynard Le Roux, Michael E. J. Lean, Barbara McGowan, Tariq Rehman, John Wilding, Gary Wittert, Ian Caterson, Joeseph Proietto, John Prins, Bruno Geloneze Neto, Jorge Luiz Gross, Antônio Roberto Chacra, Alfredo Halpern, Henrique Suplicy, Francis Chun Chung Chow, Hemant Thacker, Manoj Chadha, Hemaraj Chandalia, AG Unnikrishnan, Sanjay Kalra, Neeta Deshpande, Minakshi Shunmugavelu, Vaishali Deshmukh, Maximo Maislos, G. Lieberman, Ilan Shimon, Naftali Stern, Dan Nabriski, Eddy Karnieli, Naim Shehadeh, Guillermo González-Gálvez, María del Rosario Arechavaleta-Granell, R. Ortiz, Guadalupe Morales Franco, Irina Gurieva, Л. А. Суплотова, Е. А. Трошина, Ludmila Ruyatkina, Emma Anatolievna Voychik, S. Yu. Martsevich, M.A. Startseva Startseva, Mary Seeber, Aysha Badat, Graham Ellis, Yüksel Altuntaş, Serdar Güler, Ender Ülgen, Tuncay Delibaşı, Tony Chetty, Randy Hart, Jeannette Janzen, Isabelle Labonté, David Lau, Joanne Liutkus, Dennis D. O’Keefe, Raj Padwal, Thomas Ransom, Richard Tytus, S. John Weisnagel, Jay Adler, Keith Aqua, Stephen Aronoff, Gary Bedel, Thomas Blevins, Joe Blumenau, Andrew Brockmyre, Robert S. Call, Rafael Canadas, Louis Chaykin, Kenneth L. Cohen, Jeffrey Keith Conrow, Matthew Davis, H. Jackson Downey, S.R. Drosman, Steven Duckor, Hayley Farmer, James J. Farrell, Stephen Fehnel, Matthew Patrick Finneran, Ray Forbes, Alan D. Forker, Mark Fredrick, Ken Fujioka, S Geller, Santosh Gill, Linda A. Glaser, Susan Neims Greco, Frank L. Greenway, Wayne L. Harper, Lee Herman, J. Hoekstra, Richard Ingebretsen, Rodney Ison, Rajeev Jain, Roy A. Kaplan, S. Kaster, Gregory Haase, Boris Kerzner, Judith L. Kirstein, William Koltun, Diane Krieger, Cora E. Lewis, Robert D. Madder, Richard N Marple, Edward J McDermott, Curtis J. Mello, Alan B. Miller, Julie Mullen, John Nardandrea, Patrick M. O’Neil, F. Xavier Pi-Sunyer, Ronald M Pucillo, Chanhaeng Rhee, Scott Redrick, Aaron Pardini, Jeffrey Rothman, Domenica Rubino, Gladstone Sellers, Timothy R. Smith, William Byars, Joseph Soufer, Allen Sussman, Kyle Patrick, Erich Lloyd Schramm, Martin van Cleeff, Saul Reuel Berg, Holly R. Wyatt, James A. Simon,

Metabolism, Diabetes, and Cancer

Background Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark.