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

Carel W. le Roux, Arne Astrup, Ken Fujioka, Frank Greenway, David C.W. Lau, Luc Van Gaal, Rafael Violante Ortiz, John P.H. Wilding, Trine V. Skjøth, Linda Shapiro Manning, Xavier Pi-Sunyer, Andreas Hamann, Alain Barakat, Matthias Blüher, Thomas Linn, Andrea Mölle, Alexander Segner, Petra Stübler, Regina Tosch-Sisting, Furio PaciniFerruccio 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 Csaszar, Barbara Zahorska-Markiewicz, Danuta Pupek-Musialik, Edward Franek, Lucyna Ostrowska, Magdalena Olszanecka-Glinianowicz, Nebojsa Lalic, Dragan Micic, Bernhard Ludvik, Bernhard Paulweber, Rudolf Prager, André Scheen, Luc Van Gaal, Arne Vernon Astrup, Kjeld Hermansen, Sten Madsbad, Aila Rissanen, Sakari Nieminen, Markku Savolainen, Michel Krempf, Monique Romon, Martine Laville, Michel Marre, Reginald Mira, Francis Finucane, Aletha Veenendaal, Frank van Berkum, Solrun Johannsson-Vidarsdóttir, Vivienne Van de Walle, Eelco Meesters, Jøran Hjelmesæth, Tor Ole Klemsdal, Bård Kulseng, Birgit Bach-Kliegel, Kurt Laederach, Lukas Villiger, Alain Golay, Stefan Bilz, Thozhukat Sathyapalan, Stephen Bain, Sudesh 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, Antonio Roberto Chacra, Alfredo Halpern, Henrique de Almeida Suplicy, Francis Chun Chung Chow, Hemant P. Thacker, Manoj Chadha, Hemaraj Chandalia, Ambika Unnikrishnan, Sanjay Kalra, Neeta Deshpande, Minakshi Shunmugavelu, Vaishali Chetan Deshmukh, Maximo Maislos, Gabriella Segal Lieberman, Ilan Shimon, Naftali Stern, Dan Nabriski, Eddy Karnieli, Naim Shehadeh, Guillermo Gonzalez-Galvez, Maria del Rosario Arechavaleta-Granell, Rafael Margarito Violante Ortiz, Guadalupe Morales Franco, Irina Gurieva, Lyudmila Aleksandrovna Suplotova, Ekaterina Troshina, Ludmila Aleksandrovna Ruyatkina, Emma Anatolievna Voychik, Sergey Martsevich, Maria A. Startseva, Mary Elizabeth Seeber, Aysha Badat, Graham Ellis, Yuksel Altuntas, Serdar Guler, Ender Ulgen, Tuncay Delibasi, Tony Chetty, Randy Hart, Jeannette Janzen, Isabelle Labonte, David Lau, Joanne Liutkus, Dennis O'Keefe, Raj Padwal, Thomas P.P. Ransom, Richard Tytus, Stanley John Weisnagel, Jay Adler, Keith Aqua, Stephen L. Aronoff, Gary W. Bedel, Thomas Craig Blevins, Joe Blumenau, Andrew Peter Brockmyre, Robert S. Call, Rafael Canadas, Louis B. Chaykin, Kenneth Cohen, Jeffrey Keith Conrow, Matthew G. Davis, H. Jackson Downey, Steven Richard Drosman, Steven Duckor, H. Frank Farmer, James Farrell, Stephen Fehnel, Matthew Patrick Finneran, Ray Forbes, Alan Forker, Mark Fredrick, Ken Fujioka, Steven Andrew Geller, Santosh Gill, Linda Glaser, Susan Neims Greco, Frank Lyons Greenway, Wayne Harper, Lee Herman, John Hoekstra, Richard Ingebretsen, Rodney Ison, Rajeev K. Jain, Roy Kaplan, Steven Richard Kaster, Gregory A. Haase, Boris Kerzner, Judith Lee Kirstein, William Koltun, Diane R. Krieger, Cora Elizabeth Lewis, Robert Madder, Richard N. Marple, Edward J. McDermott, Curtis John Mello, Alan B. Miller, Julie Mullen, John Nardandrea, Patrick O'Neil, F. Xavier Pi-Sunyer, Ronald M. Pucillo, Chanhaeng Rhee, Scott Redrick, Aaron Pardini, Jeffrey Rothman, Domenica Marie Rubino, Gladstone Sellers, Timothy Smith, William David Byars, Joseph Soufer, Allen Michael Sussman, Kyle Patrick, Erich Lloyd Schramm, Martin Van Cleeff, Saul Reuel Berg, Holly Roxanna Wyatt, James Alan Simon

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1399-1409
Number of pages11
JournalThe Lancet
Volume389
Issue number10077
DOIs
Publication statusPublished - Apr 8 2017

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ASJC Scopus subject areas

  • Medicine(all)

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