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

Research output: Contribution to journalArticle

126 Citations (Scopus)

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
StatePublished - Apr 8 2017

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Prediabetic State
Risk Reduction Behavior
Type 2 Diabetes Mellitus
Placebos
Weights and Measures
Obesity
Liraglutide
Insurance Benefits
Denmark
Therapeutics
Random Allocation
Telephone
Comorbidity
Weight Loss
Body Mass Index
Exercise
Diet

ASJC Scopus subject areas

  • Medicine(all)

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

In: The Lancet, Vol. 389, No. 10077, 08.04.2017, p. 1399-1409.

Research output: Contribution to journalArticle

le Roux, CW, Astrup, A, Fujioka, K, Greenway, F, Lau, DCW, Van Gaal, L, Ortiz, RV, Wilding, JPH, Skjøth, TV, Manning, LS, Pi-Sunyer, X, Hamann, A, Barakat, A, Blüher, M, Linn, T, Mölle, A, Segner, A, Stübler, P, Tosch-Sisting, R, Pacini, F, Santini, F, Marchesini, G, Rotella, CM, Invitti, C, Vettor, R, Buscemi, S, Raya, PM, Freijoo, FC, de Barbará, RG, Carraro, R, Bobillo, ER, de la Cuesta, C, Farsang, C, Csaszar, A, Zahorska-Markiewicz, B, Pupek-Musialik, D, Franek, E, Ostrowska, L, Olszanecka-Glinianowicz, M, Lalic, N, Micic, D, Ludvik, B, Paulweber, B, Prager, R, Scheen, A, Van Gaal, L, Astrup, AV, Hermansen, K, Madsbad, S, Rissanen, A, Nieminen, S, Savolainen, M, Krempf, M, Romon, M, Laville, M, Marre, M, Mira, R, Finucane, F, Veenendaal, A, van Berkum, F, Johannsson-Vidarsdóttir, S, Van de Walle, V, Meesters, E, Hjelmesæth, J, Klemsdal, TO, Kulseng, B, Bach-Kliegel, B, Laederach, K, Villiger, L, Golay, A, Bilz, S, Sathyapalan, T, Bain, S, Kumar, S, Le Roux, CW, Lean, MEJ, McGowan, B, Rehman, T, Wilding, J, Wittert, G, Caterson, I, Proietto, J, Prins, J, Neto, BG, Gross, JL, Chacra, AR, Halpern, A, de Almeida Suplicy, H, Chow, FCC, Thacker, HP, Chadha, M, Chandalia, H, Unnikrishnan, A, Kalra, S, Deshpande, N, Shunmugavelu, M, Deshmukh, VC, Maislos, M, Lieberman, GS, Shimon, I, Stern, N, Nabriski, D, Karnieli, E, Shehadeh, N, Gonzalez-Galvez, G, del Rosario Arechavaleta-Granell, M, Ortiz, RMV, Franco, GM, Gurieva, I, Suplotova, LA, Troshina, E, Ruyatkina, LA, Voychik, EA, Martsevich, S, Startseva, MA, Seeber, ME, Badat, A, Ellis, G, Altuntas, Y, Guler, S, Ulgen, E, Delibasi, T, Chetty, T, Hart, R, Janzen, J, Labonte, I, Lau, D, Liutkus, J, O'Keefe, D, Padwal, R, Ransom, TPP, Tytus, R, Weisnagel, SJ, Adler, J, Aqua, K, Aronoff, SL, Bedel, GW, Blevins, TC, Blumenau, J, Brockmyre, AP, Call, RS, Canadas, R, Chaykin, LB, Cohen, K, Conrow, JK, Davis, MG, Downey, HJ, Drosman, SR, Duckor, S, Farmer, HF, Farrell, J, Fehnel, S, Finneran, MP, Forbes, R, Forker, A, Fredrick, M, Fujioka, K, Geller, SA, Gill, S, Glaser, L, Greco, SN, Greenway, FL, Harper, W, Herman, L, Hoekstra, J, Ingebretsen, R, Ison, R, Jain, RK, Kaplan, R, Kaster, SR, Haase, GA, Kerzner, B, Kirstein, JL, Koltun, W, Krieger, DR, Lewis, CE, Madder, R, Marple, RN, McDermott, EJ, Mello, CJ, Miller, AB, Mullen, J, Nardandrea, J, O'Neil, P, Pi-Sunyer, FX, Pucillo, RM, Rhee, C, Redrick, S, Pardini, A, Rothman, J, Rubino, DM, Sellers, G, Smith, T, Byars, WD, Soufer, J, Sussman, AM, Patrick, K, Schramm, EL, Van Cleeff, M, Berg, SR, Wyatt, HR & Simon, JA 2017, '3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial', The Lancet, vol. 389, no. 10077, pp. 1399-1409. https://doi.org/10.1016/S0140-6736(17)30069-7
le Roux, Carel W. ; Astrup, Arne ; Fujioka, Ken ; Greenway, Frank ; Lau, David C.W. ; Van Gaal, Luc ; Ortiz, Rafael Violante ; Wilding, John P.H. ; Skjøth, Trine V. ; Manning, Linda Shapiro ; Pi-Sunyer, Xavier ; Hamann, Andreas ; Barakat, Alain ; Blüher, Matthias ; Linn, Thomas ; Mölle, Andrea ; Segner, Alexander ; Stübler, Petra ; Tosch-Sisting, Regina ; Pacini, Furio ; Santini, Ferruccio ; Marchesini, Giulio ; Rotella, Carlo Maria ; Invitti, Cecilia ; Vettor, Roberto ; Buscemi, Silvio ; Raya, Pedro Mezquita ; Freijoo, Felipe Casanueva ; de Barbará, Ramón Gomis ; Carraro, Raffaele ; Bobillo, Enrique Romero ; de la Cuesta, Carmen ; Farsang, Csaba ; Csaszar, Albert ; Zahorska-Markiewicz, Barbara ; Pupek-Musialik, Danuta ; Franek, Edward ; Ostrowska, Lucyna ; Olszanecka-Glinianowicz, Magdalena ; Lalic, Nebojsa ; Micic, Dragan ; Ludvik, Bernhard ; Paulweber, Bernhard ; Prager, Rudolf ; Scheen, André ; Van Gaal, Luc ; Astrup, Arne Vernon ; Hermansen, Kjeld ; Madsbad, Sten ; Rissanen, Aila ; Nieminen, Sakari ; Savolainen, Markku ; Krempf, Michel ; Romon, Monique ; Laville, Martine ; Marre, Michel ; Mira, Reginald ; Finucane, Francis ; Veenendaal, Aletha ; van Berkum, Frank ; Johannsson-Vidarsdóttir, Solrun ; Van de Walle, Vivienne ; Meesters, Eelco ; Hjelmesæth, Jøran ; Klemsdal, Tor Ole ; Kulseng, Bård ; Bach-Kliegel, Birgit ; Laederach, Kurt ; Villiger, Lukas ; Golay, Alain ; Bilz, Stefan ; Sathyapalan, Thozhukat ; Bain, Stephen ; Kumar, Sudesh ; Le Roux, Carel Wynard ; Lean, Michael E.J. ; McGowan, Barbara ; Rehman, Tariq ; Wilding, John ; Wittert, Gary ; Caterson, Ian ; Proietto, Joeseph ; Prins, John ; Neto, Bruno Geloneze ; Gross, Jorge Luiz ; Chacra, Antonio Roberto ; Halpern, Alfredo ; de Almeida Suplicy, Henrique ; Chow, Francis Chun Chung ; Thacker, Hemant P. ; Chadha, Manoj ; Chandalia, Hemaraj ; Unnikrishnan, Ambika ; Kalra, Sanjay ; Deshpande, Neeta ; Shunmugavelu, Minakshi ; Deshmukh, Vaishali Chetan ; Maislos, Maximo ; Lieberman, Gabriella Segal ; Shimon, Ilan ; Stern, Naftali ; Nabriski, Dan ; Karnieli, Eddy ; Shehadeh, Naim ; Gonzalez-Galvez, Guillermo ; del Rosario Arechavaleta-Granell, Maria ; Ortiz, Rafael Margarito Violante ; Franco, Guadalupe Morales ; Gurieva, Irina ; Suplotova, Lyudmila Aleksandrovna ; Troshina, Ekaterina ; Ruyatkina, Ludmila Aleksandrovna ; Voychik, Emma Anatolievna ; Martsevich, Sergey ; Startseva, Maria A. ; Seeber, Mary Elizabeth ; Badat, Aysha ; Ellis, Graham ; Altuntas, Yuksel ; Guler, Serdar ; Ulgen, Ender ; Delibasi, Tuncay ; Chetty, Tony ; Hart, Randy ; Janzen, Jeannette ; Labonte, Isabelle ; Lau, David ; Liutkus, Joanne ; O'Keefe, Dennis ; Padwal, Raj ; Ransom, Thomas P.P. ; Tytus, Richard ; Weisnagel, Stanley John ; Adler, Jay ; Aqua, Keith ; Aronoff, Stephen L. ; Bedel, Gary W. ; Blevins, Thomas Craig ; Blumenau, Joe ; Brockmyre, Andrew Peter ; Call, Robert S. ; Canadas, Rafael ; Chaykin, Louis B. ; Cohen, Kenneth ; Conrow, Jeffrey Keith ; Davis, Matthew G. ; Downey, H. Jackson ; Drosman, Steven Richard ; Duckor, Steven ; Farmer, H. Frank ; Farrell, James ; Fehnel, Stephen ; Finneran, Matthew Patrick ; Forbes, Ray ; Forker, Alan ; Fredrick, Mark ; Fujioka, Ken ; Geller, Steven Andrew ; Gill, Santosh ; Glaser, Linda ; Greco, Susan Neims ; Greenway, Frank Lyons ; Harper, Wayne ; Herman, Lee ; Hoekstra, John ; Ingebretsen, Richard ; Ison, Rodney ; Jain, Rajeev K. ; Kaplan, Roy ; Kaster, Steven Richard ; Haase, Gregory A. ; Kerzner, Boris ; Kirstein, Judith Lee ; Koltun, William ; Krieger, Diane R. ; Lewis, Cora Elizabeth ; Madder, Robert ; Marple, Richard N. ; McDermott, Edward J. ; Mello, Curtis John ; Miller, Alan B. ; Mullen, Julie ; Nardandrea, John ; O'Neil, Patrick ; Pi-Sunyer, F. Xavier ; Pucillo, Ronald M. ; Rhee, Chanhaeng ; Redrick, Scott ; Pardini, Aaron ; Rothman, Jeffrey ; Rubino, Domenica Marie ; Sellers, Gladstone ; Smith, Timothy ; Byars, William David ; Soufer, Joseph ; Sussman, Allen Michael ; Patrick, Kyle ; Schramm, Erich Lloyd ; Van Cleeff, Martin ; Berg, Saul Reuel ; Wyatt, Holly Roxanna ; Simon, James Alan. / 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes : a randomised, double-blind trial. In: The Lancet. 2017 ; Vol. 389, No. 10077. pp. 1399-1409.
@article{323c88623daf47cebf3a4cf2672efcf2,
title = "3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial",
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.",
author = "{le Roux}, {Carel W.} and Arne Astrup and Ken Fujioka and Frank Greenway and Lau, {David C.W.} and {Van Gaal}, Luc and Ortiz, {Rafael Violante} and Wilding, {John P.H.} and Skj{\o}th, {Trine V.} and Manning, {Linda Shapiro} and Xavier Pi-Sunyer and Andreas Hamann and Alain Barakat and Matthias Bl{\"u}her and Thomas Linn and Andrea M{\"o}lle and Alexander Segner and Petra St{\"u}bler and Regina Tosch-Sisting and Furio Pacini and Ferruccio Santini and Giulio Marchesini and Rotella, {Carlo Maria} and Cecilia Invitti and Roberto Vettor and Silvio Buscemi and Raya, {Pedro Mezquita} and Freijoo, {Felipe Casanueva} and {de Barbar{\'a}}, {Ram{\'o}n Gomis} and Raffaele Carraro and Bobillo, {Enrique Romero} and {de la Cuesta}, Carmen and Csaba Farsang and Albert Csaszar and Barbara Zahorska-Markiewicz and Danuta Pupek-Musialik and Edward Franek and Lucyna Ostrowska and Magdalena Olszanecka-Glinianowicz and Nebojsa Lalic and Dragan Micic and Bernhard Ludvik and Bernhard Paulweber and Rudolf Prager and Andr{\'e} Scheen and {Van Gaal}, Luc and Astrup, {Arne Vernon} and Kjeld Hermansen and Sten Madsbad and Aila Rissanen and Sakari Nieminen and Markku Savolainen and Michel Krempf and Monique Romon and Martine Laville and Michel Marre and Reginald Mira and Francis Finucane and Aletha Veenendaal and {van Berkum}, Frank and Solrun Johannsson-Vidarsd{\'o}ttir and {Van de Walle}, Vivienne and Eelco Meesters and J{\o}ran Hjelmes{\ae}th and Klemsdal, {Tor Ole} and B{\aa}rd Kulseng and Birgit Bach-Kliegel and Kurt Laederach and Lukas Villiger and Alain Golay and Stefan Bilz and Thozhukat Sathyapalan and Stephen Bain and Sudesh Kumar and {Le Roux}, {Carel Wynard} and Lean, {Michael E.J.} and Barbara McGowan and Tariq Rehman and John Wilding and Gary Wittert and Ian Caterson and Joeseph Proietto and John Prins and Neto, {Bruno Geloneze} and Gross, {Jorge Luiz} and Chacra, {Antonio Roberto} and Alfredo Halpern and {de Almeida Suplicy}, Henrique and Chow, {Francis Chun Chung} and Thacker, {Hemant P.} and Manoj Chadha and Hemaraj Chandalia and Ambika Unnikrishnan and Sanjay Kalra and Neeta Deshpande and Minakshi Shunmugavelu and Deshmukh, {Vaishali Chetan} and Maximo Maislos and Lieberman, {Gabriella Segal} and Ilan Shimon and Naftali Stern and Dan Nabriski and Eddy Karnieli and Naim Shehadeh and Guillermo Gonzalez-Galvez and {del Rosario Arechavaleta-Granell}, Maria and Ortiz, {Rafael Margarito Violante} and Franco, {Guadalupe Morales} and Irina Gurieva and Suplotova, {Lyudmila Aleksandrovna} and Ekaterina Troshina and Ruyatkina, {Ludmila Aleksandrovna} and Voychik, {Emma Anatolievna} and Sergey Martsevich and Startseva, {Maria A.} and Seeber, {Mary Elizabeth} and Aysha Badat and Graham Ellis and Yuksel Altuntas and Serdar Guler and Ender Ulgen and Tuncay Delibasi and Tony Chetty and Randy Hart and Jeannette Janzen and Isabelle Labonte and David Lau and Joanne Liutkus and Dennis O'Keefe and Raj Padwal and Ransom, {Thomas P.P.} and Richard Tytus and Weisnagel, {Stanley John} and Jay Adler and Keith Aqua and Aronoff, {Stephen L.} and Bedel, {Gary W.} and Blevins, {Thomas Craig} and Joe Blumenau and Brockmyre, {Andrew Peter} and Call, {Robert S.} and Rafael Canadas and Chaykin, {Louis B.} and Kenneth Cohen and Conrow, {Jeffrey Keith} and Davis, {Matthew G.} and Downey, {H. Jackson} and Drosman, {Steven Richard} and Steven Duckor and Farmer, {H. Frank} and James Farrell and Stephen Fehnel and Finneran, {Matthew Patrick} and Ray Forbes and Alan Forker and Mark Fredrick and Ken Fujioka and Geller, {Steven Andrew} and Santosh Gill and Linda Glaser and Greco, {Susan Neims} and Greenway, {Frank Lyons} and Wayne Harper and Lee Herman and John Hoekstra and Richard Ingebretsen and Rodney Ison and Jain, {Rajeev K.} and Roy Kaplan and Kaster, {Steven Richard} and Haase, {Gregory A.} and Boris Kerzner and Kirstein, {Judith Lee} and William Koltun and Krieger, {Diane R.} and Lewis, {Cora Elizabeth} and Robert Madder and Marple, {Richard N.} and McDermott, {Edward J.} and Mello, {Curtis John} and Miller, {Alan B.} and Julie Mullen and John Nardandrea and Patrick O'Neil and Pi-Sunyer, {F. Xavier} and Pucillo, {Ronald M.} and Chanhaeng Rhee and Scott Redrick and Aaron Pardini and Jeffrey Rothman and Rubino, {Domenica Marie} and Gladstone Sellers and Timothy Smith and Byars, {William David} and Joseph Soufer and Sussman, {Allen Michael} and Kyle Patrick and Schramm, {Erich Lloyd} and {Van Cleeff}, Martin and Berg, {Saul Reuel} and Wyatt, {Holly Roxanna} and Simon, {James Alan}",
year = "2017",
month = "4",
day = "8",
doi = "10.1016/S0140-6736(17)30069-7",
language = "English (US)",
volume = "389",
pages = "1399--1409",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10077",

}

TY - JOUR

T1 - 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes

T2 - a randomised, double-blind trial

AU - le Roux, Carel W.

AU - Astrup, Arne

AU - Fujioka, Ken

AU - Greenway, Frank

AU - Lau, David C.W.

AU - Van Gaal, Luc

AU - Ortiz, Rafael Violante

AU - Wilding, John P.H.

AU - Skjøth, Trine V.

AU - Manning, Linda Shapiro

AU - Pi-Sunyer, Xavier

AU - Hamann, Andreas

AU - Barakat, Alain

AU - Blüher, Matthias

AU - Linn, Thomas

AU - Mölle, Andrea

AU - Segner, Alexander

AU - Stübler, Petra

AU - Tosch-Sisting, Regina

AU - Pacini, Furio

AU - Santini, Ferruccio

AU - Marchesini, Giulio

AU - Rotella, Carlo Maria

AU - Invitti, Cecilia

AU - Vettor, Roberto

AU - Buscemi, Silvio

AU - Raya, Pedro Mezquita

AU - Freijoo, Felipe Casanueva

AU - de Barbará, Ramón Gomis

AU - Carraro, Raffaele

AU - Bobillo, Enrique Romero

AU - de la Cuesta, Carmen

AU - Farsang, Csaba

AU - Csaszar, Albert

AU - Zahorska-Markiewicz, Barbara

AU - Pupek-Musialik, Danuta

AU - Franek, Edward

AU - Ostrowska, Lucyna

AU - Olszanecka-Glinianowicz, Magdalena

AU - Lalic, Nebojsa

AU - Micic, Dragan

AU - Ludvik, Bernhard

AU - Paulweber, Bernhard

AU - Prager, Rudolf

AU - Scheen, André

AU - Van Gaal, Luc

AU - Astrup, Arne Vernon

AU - Hermansen, Kjeld

AU - Madsbad, Sten

AU - Rissanen, Aila

AU - Nieminen, Sakari

AU - Savolainen, Markku

AU - Krempf, Michel

AU - Romon, Monique

AU - Laville, Martine

AU - Marre, Michel

AU - Mira, Reginald

AU - Finucane, Francis

AU - Veenendaal, Aletha

AU - van Berkum, Frank

AU - Johannsson-Vidarsdóttir, Solrun

AU - Van de Walle, Vivienne

AU - Meesters, Eelco

AU - Hjelmesæth, Jøran

AU - Klemsdal, Tor Ole

AU - Kulseng, Bård

AU - Bach-Kliegel, Birgit

AU - Laederach, Kurt

AU - Villiger, Lukas

AU - Golay, Alain

AU - Bilz, Stefan

AU - Sathyapalan, Thozhukat

AU - Bain, Stephen

AU - Kumar, Sudesh

AU - Le Roux, Carel Wynard

AU - Lean, Michael E.J.

AU - McGowan, Barbara

AU - Rehman, Tariq

AU - Wilding, John

AU - Wittert, Gary

AU - Caterson, Ian

AU - Proietto, Joeseph

AU - Prins, John

AU - Neto, Bruno Geloneze

AU - Gross, Jorge Luiz

AU - Chacra, Antonio Roberto

AU - Halpern, Alfredo

AU - de Almeida Suplicy, Henrique

AU - Chow, Francis Chun Chung

AU - Thacker, Hemant P.

AU - Chadha, Manoj

AU - Chandalia, Hemaraj

AU - Unnikrishnan, Ambika

AU - Kalra, Sanjay

AU - Deshpande, Neeta

AU - Shunmugavelu, Minakshi

AU - Deshmukh, Vaishali Chetan

AU - Maislos, Maximo

AU - Lieberman, Gabriella Segal

AU - Shimon, Ilan

AU - Stern, Naftali

AU - Nabriski, Dan

AU - Karnieli, Eddy

AU - Shehadeh, Naim

AU - Gonzalez-Galvez, Guillermo

AU - del Rosario Arechavaleta-Granell, Maria

AU - Ortiz, Rafael Margarito Violante

AU - Franco, Guadalupe Morales

AU - Gurieva, Irina

AU - Suplotova, Lyudmila Aleksandrovna

AU - Troshina, Ekaterina

AU - Ruyatkina, Ludmila Aleksandrovna

AU - Voychik, Emma Anatolievna

AU - Martsevich, Sergey

AU - Startseva, Maria A.

AU - Seeber, Mary Elizabeth

AU - Badat, Aysha

AU - Ellis, Graham

AU - Altuntas, Yuksel

AU - Guler, Serdar

AU - Ulgen, Ender

AU - Delibasi, Tuncay

AU - Chetty, Tony

AU - Hart, Randy

AU - Janzen, Jeannette

AU - Labonte, Isabelle

AU - Lau, David

AU - Liutkus, Joanne

AU - O'Keefe, Dennis

AU - Padwal, Raj

AU - Ransom, Thomas P.P.

AU - Tytus, Richard

AU - Weisnagel, Stanley John

AU - Adler, Jay

AU - Aqua, Keith

AU - Aronoff, Stephen L.

AU - Bedel, Gary W.

AU - Blevins, Thomas Craig

AU - Blumenau, Joe

AU - Brockmyre, Andrew Peter

AU - Call, Robert S.

AU - Canadas, Rafael

AU - Chaykin, Louis B.

AU - Cohen, Kenneth

AU - Conrow, Jeffrey Keith

AU - Davis, Matthew G.

AU - Downey, H. Jackson

AU - Drosman, Steven Richard

AU - Duckor, Steven

AU - Farmer, H. Frank

AU - Farrell, James

AU - Fehnel, Stephen

AU - Finneran, Matthew Patrick

AU - Forbes, Ray

AU - Forker, Alan

AU - Fredrick, Mark

AU - Fujioka, Ken

AU - Geller, Steven Andrew

AU - Gill, Santosh

AU - Glaser, Linda

AU - Greco, Susan Neims

AU - Greenway, Frank Lyons

AU - Harper, Wayne

AU - Herman, Lee

AU - Hoekstra, John

AU - Ingebretsen, Richard

AU - Ison, Rodney

AU - Jain, Rajeev K.

AU - Kaplan, Roy

AU - Kaster, Steven Richard

AU - Haase, Gregory A.

AU - Kerzner, Boris

AU - Kirstein, Judith Lee

AU - Koltun, William

AU - Krieger, Diane R.

AU - Lewis, Cora Elizabeth

AU - Madder, Robert

AU - Marple, Richard N.

AU - McDermott, Edward J.

AU - Mello, Curtis John

AU - Miller, Alan B.

AU - Mullen, Julie

AU - Nardandrea, John

AU - O'Neil, Patrick

AU - Pi-Sunyer, F. Xavier

AU - Pucillo, Ronald M.

AU - Rhee, Chanhaeng

AU - Redrick, Scott

AU - Pardini, Aaron

AU - Rothman, Jeffrey

AU - Rubino, Domenica Marie

AU - Sellers, Gladstone

AU - Smith, Timothy

AU - Byars, William David

AU - Soufer, Joseph

AU - Sussman, Allen Michael

AU - Patrick, Kyle

AU - Schramm, Erich Lloyd

AU - Van Cleeff, Martin

AU - Berg, Saul Reuel

AU - Wyatt, Holly Roxanna

AU - Simon, James Alan

PY - 2017/4/8

Y1 - 2017/4/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85013371919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013371919&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(17)30069-7

DO - 10.1016/S0140-6736(17)30069-7

M3 - Article

C2 - 28237263

AN - SCOPUS:85013371919

VL - 389

SP - 1399

EP - 1409

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10077

ER -