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 Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation.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 language | English (US) |
|---|---|
| Pages (from-to) | 1399-1409 |
| Number of pages | 11 |
| Journal | The Lancet |
| Volume | 389 |
| Issue number | 10077 |
| DOIs | |
| Publication status | Published - Apr 8 2017 |
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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 journal › Article
}
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 -