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, C. W.; Astrup, A.; Fujioka, K.; Greenway, F.; Lau, D. C. W.; Van Gaal, L.; Ortiz, R. V.; Wilding, J. P. H.; Skjøth, T. V.; Manning, L. S.; 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, C. M.; Invitti, C.; Vettor, R.; Buscemi, S.; Raya, P. M.; Freijoo, F. C.; de Barbará, R. G.; Carraro, R.; Bobillo, E. R.; 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, André; Astrup, A. V.; 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, T. O.; Kulseng, B.; Bach-Kliegel, B.; Laederach, K.; Villiger, L.; Golay, A.; Bilz, S.; Sathyapalan, T.; Bain, S.; Kumar, S.; Lean, M. E. J.; McGowan, B.; Rehman, T.; Wilding, J.; Wittert, G.; Caterson, I.; Proietto, J.; Prins, J.; Neto, B. G.; Gross, J. L.; Chacra, A. R.; Halpern, A.; de Almeida Suplicy, H.; Chow, F. C. C.; Thacker, H. P.; Chadha, M.; Chandalia, H.; Unnikrishnan, A.; Kalra, S.; Deshpande, N.; Shunmugavelu, M.; Deshmukh, V. C.; Maislos, M.; Lieberman, G. S.; Shimon, I.; Stern, N.; Nabriski, D.; Karnieli, E.; Shehadeh, N.; Gonzalez-Galvez, G.; del Rosario Arechavaleta-Granell, M.; Ortiz, R. M. V.; Franco, G. M.; Gurieva, I.; Suplotova, L. A.; Troshina, E.; Ruyatkina, L. A.; Voychik, E. A.; Martsevich, S.; Startseva, M. A.; Seeber, M. E.; 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, T. P. P.; Tytus, R.; Weisnagel, S. J.; Adler, J.; Aqua, K.; Aronoff, S. L.; Bedel, G. W.; Blevins, T. C.; Blumenau, J.; Brockmyre, A. P.; Call, R. S.; Canadas, R.; Chaykin, L. B.; Cohen, K.; Conrow, J. K.; Davis, M. G.; Downey, H. J.; Drosman, S. R.; Duckor, S.; Farmer, H. F.; Farrell, J.; Fehnel, S.; Finneran, M. P.; Forbes, R.; Forker, A.; Fredrick, M.; Geller, S. A.; Gill, S.; Glaser, L.; Greco, S. N.; Greenway, F. L.; Harper, W.; Herman, L.; Hoekstra, J.; Ingebretsen, R.; Ison, R.; Jain, R. K.; Kaplan, R.; Kaster, S. R.; Haase, G. A.; Kerzner, B.; Kirstein, J. L.; Koltun, W.; Krieger, D. R.; Lewis, C. E.; Madder, R.; Marple, R. N.; McDermott, E. J.; Mello, C. J.; Miller, A. B.; Mullen, J.; Nardandrea, J.; O'Neil, P.; Pi-Sunyer, F. X.; Pucillo, R. M.; Rhee, C.; Redrick, S.; Pardini, A.; Rothman, J.; Rubino, D. M.; Sellers, G.; Smith, T.; Byars, W. D.; Soufer, J.; Sussman, A. M.; Patrick, K.; Schramm, E. L.; Van Cleeff, M.; Berg, S. R.; Wyatt, H. R.; Simon, Justine

doi:10.1016/S0140-6736(17)30069-7

Article (Scientific journals)

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, C. W.; Astrup, A.; Fujioka, K. et al.

2017 • In The Lancet, 389 (10077), p. 1399-1409

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https://hdl.handle.net/2268/229819

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

PubMed
28237263

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Keywords :

GLP1R protein, human; Article; Adult; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Injections, Subcutaneous; Liraglutide; Male; Middle Aged; Obesity; Placebos; Prediabetic State; Risk Reduction Behavior; Treatment Outcome; Weight Loss

Abstract :

[en] 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. © 2017 Elsevier Ltd

Disciplines :

Pharmacy, pharmacology & toxicology
Endocrinology, metabolism & nutrition

Author, co-author :

Le Roux, C. W.; Diabetes Complications Research Centre, Conway Institute, University College Dublin, Ireland, Investigative Science, Imperial College London, London, United Kingdom

Astrup, A.; Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark

Fujioka, K.; Division of Endocrinology, Department of Nutrition and Metabolic Research, Scripps Clinic, La Jolla, CA, United States

Greenway, F.; Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, CA, United States

Lau, D. C. W.; Departments of Medicine and Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada

Van Gaal, L.; Department of Endocrinology, Diabetology and Metabolic Diseases, Antwerp University Hospital, Antwerp, Belgium

Ortiz, R. V.; Departamento Endocrinología, Instituto Mexicano del Seguro Social, Ciudad Madero, Mexico

Wilding, J. P. H.; Department of Obesity and Endocrinology, University of Liverpool, Liverpool, United Kingdom

Skjøth, T. V.; Novo Nordisk A/S, Soeborg, Denmark

Manning, L. S.; Novo Nordisk A/S, Soeborg, Denmark

More authors (189 more)

Language :

English

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

Publication date :

2017

Journal title :

The Lancet

ISSN :

0140-6736

eISSN :

1474-547X

Publisher :

Lancet Publishing Group

Volume :

389

Issue :

10077

Pages :

1399-1409

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 03 December 2018

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