A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Authors: Pedro Mezquita Raya
Bernhard Ludvik
Thomas Linn
Kurt Laederach
Gabriella Segal Lieberman
Sakari Nieminen
Naftali Stern
Sergey Martsevich
Tony Chetty
Dragan Micic
Danuta Pupek-Musialik
Steven Duckor
Boris Kerzner
David Lau
Matthew G Davis
Alexander Segner
Vivienne Van de Walle
John Hoekstra
Gregory A Haase
Edward Franek
Maximo Maislos
Albert Csaszar
Joanne Liutkus
Cecilia Invitti
Markku Savolainen
Manoj Chadha
Aaron Pardini
Frank Greenway
Ronald M Pucillo
Cora Elizabeth Lewis
Petra Stübler
Rafael Margarito Violante Ortiz
Carlo Maria Rotella
Antonio Roberto Chacra
Rajeev K Jain
Vaishali Chetan Deshmukh
Raffaele Carraro
David C W Lau
Alan Forker
Mark Fredrick
Nebojsa Lalic
Dennis O&#x27;Keefe
F  Xavier Pi-Sunyer
Monique Romon
Francis Finucane
Steven Andrew Geller
Ramón Gomis de Barbará
Csaba Farsang
H  Frank Farmer
John Wilding
Jorge Luiz Gross
Eddy Karnieli
Birgit Bach-Kliegel
Santosh Gill
Furio Pacini
Arne Astrup
Ekaterina Troshina
Steven Richard Kaster
Richard Tytus
Michael E J Lean
Jeffrey Rothman
Rafael Canadas
Rodney Ison
Joeseph Proietto
Julie Mullen
Martine Laville
Ray Forbes
Ken Fujioka
Enrique Romero Bobillo
Michel Marre
Hemant P Thacker
Irina Gurieva
Bruno Geloneze Neto
Sten Madsbad
Maria del Rosario Arechavaleta-Granell
Tor Ole Klemsdal
Tuncay Delibasi
Richard Ingebretsen
Hemaraj Chandalia
Jøran Hjelmesæth
Serdar Guler
Stanley John Weisnagel
Solrun Johannsson-Vidarsdóttir
Guadalupe Morales Franco
Rudolf Prager
Alan B Miller
Alfredo Halpern
Lukas Villiger
Luc Van Gaal
Andrew Peter Brockmyre
James Farrell
Raj Padwal
Thomas Craig Blevins
Sanjay Kalra
Bård Kulseng
Joseph Soufer
Carmen de la Cuesta
Felipe Casanueva Freijoo
Timothy Smith
Martin Van Cleeff
Reginald Mira
Naim Shehadeh
Joe Blumenau
Rafael Violante Ortiz
James Alan Simon
Regina Tosch-Sisting
Gary Wittert
Yuksel Altuntas
Neeta Deshpande
Magdalena Olszanecka-Glinianowicz
John Nardandrea
Patrick O&#x27;Neil
Barbara Zahorska-Markiewicz
Alain Golay
Keith Aqua
Tariq Rehman
Louis B Chaykin
Mary Elizabeth Seeber
Stephen Fehnel
Chanhaeng Rhee
Aletha Veenendaal
William David Byars
Stephen Bain
Guillermo Gonzalez-Galvez
Richard N Marple
Frank van Berkum
Henrique de Almeida Suplicy
Judith Lee Kirstein
Bernhard Paulweber
Wayne Harper
Minakshi Shunmugavelu
Domenica Marie Rubino
Allen Michael Sussman
Frank Lyons Greenway
Roberto Vettor
John P H Wilding
Thozhukat Sathyapalan
Eelco Meesters
William Koltun
Thomas P P Ransom
Lucyna Ostrowska
Diane R Krieger
Carel W le Roux
Francis Chun Chung Chow
Arne Vernon Astrup
Aila Rissanen
Erich Lloyd Schramm
Giulio Marchesini
Carel Wynard Le Roux
Ambika Unnikrishnan
Matthew Patrick Finneran
Maria A Startseva
Holly Roxanna Wyatt
Stefan Bilz
Ian Caterson
André Scheen
Linda Glaser
Kenneth Cohen
Edward J McDermott
Alain Barakat
Steven Richard Drosman
Jay Adler
Scott Redrick
Andrea Mölle
Ludmila Aleksandrovna Ruyatkina
John Prins
Dan Nabriski
Curtis John Mello
Isabelle Labonte
Graham Ellis
Silvio Buscemi
Xavier Pi-Sunyer
Kjeld Hermansen
Matthias Blüher
Gladstone Sellers
Stephen L Aronoff
Lee Herman
Aysha Badat
Jeffrey Keith Conrow
Kyle Patrick
H Jackson Downey
Susan Neims Greco
Roy Kaplan
Christine Bjørn Jensen
Michel Krempf
Robert Madder
Ferruccio Santini
Randy Hart
SCALE Obesity and Prediabetes NN8022-1839 Study Group
Saul Reuel Berg
Gary W Bedel
Lyudmila Aleksandrovna Suplotova
Ender Ulgen
Emma Anatolievna Voychik
Andreas Hamann
Ilan Shimon
Barbara McGowan
Jeannette Janzen
Sudesh Kumar
Robert S Call
Journal: New England Journal of Medicine (2015)
Discipline: CLINICAL MEDICINE
Keywords: Obesity; Liraglutide; Weight loss; Lifestyle intervention; Body weight
Affiliations: From the Division of Endocrinology and Obesity Research Center, Columbia University, New York (X.P.-S.); Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg (A.A.), and Novo Nordisk, Søborg (C.B.J.) - both in Denmark; Department of Nutrition and Metabolic Research, Division of Endocrinology, Scripps Clinic, La Jolla, CA (K.F.); Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge (F.G.); Obesity and Metabolic Syndrome Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, University of São Paulo Medical School, São Paulo (A.H.); Clinique d'Endocrinologie et Nutrition, Centre Hospitalier Universitaire, Nantes, France (M.K.); Departments of Medicine and Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada (D.C.W.L.); Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin (C.W.R.); Departamento Endocrinología, Instituto Mexicano del Seguro Social, Cuidad Madero, Mexico (R.V.O.); and Department of Obesity and Endocrinology, University of Liverpool, Liverpool, United Kingdom (J.P.H.W.).

Abstract:  Background: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. Methods: We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. Results: At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. Conclusions: In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.). 

Retracted: No

PubPeer comments:
 u2022tLast observation carried forward likely favours more toxic drugs (Molnar et al. 2008). u2022t2:1 drug group:placebo group u2013 not equal opportunity for the placebo group results to compete with the Liraglutide group results for weight loss because there are twice as many participants in this group. u2022tStatistical analysis u2013 Novo Nordisk sponsored and funded this trial and stood to financially benefit from the success of this drug. Novo Nordisk planned and performed the statistical analyses, provided editorial and writing assistance and provided the trial drugs. Possible bias in favour of use of Liraglutide for weight loss could have played a role in the statistical analyses and writing of this publication. u2022tHypoglycaemic events not included in Table 3. u2018Adverse Events and Serious Adverse Eventsu2019 ,