A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Xavier Pi-Sunyer, Arne Astrup, Ken Fujioka, Frank Greenway, Alfredo Halpern, Michel Krempf, David C W Lau, Carel W le Roux, Rafael Violante Ortiz, Christine Bjørn Jensen, John P H Wilding, SCALE Obesity and Prediabetes NN8022-1839 Study Group, Andreas Hamann, Alain Barakat, Matthias Blüher, Thomas Linn, Andrea Mölle, Alexander Segner, Petra Stübler, Regina Tosch-Sisting, Furio Pacini, Ferruccio 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, Xavier Pi-Sunyer, Arne Astrup, Ken Fujioka, Frank Greenway, Alfredo Halpern, Michel Krempf, David C W Lau, Carel W le Roux, Rafael Violante Ortiz, Christine Bjørn Jensen, John P H Wilding, SCALE Obesity and Prediabetes NN8022-1839 Study Group, Andreas Hamann, Alain Barakat, Matthias Blüher, Thomas Linn, Andrea Mölle, Alexander Segner, Petra Stübler, Regina Tosch-Sisting, Furio Pacini, Ferruccio 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
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<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<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<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.).
Source: PubMed