3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

• Published in: The Lancet (British edition) Vol. 389; no. 10077; pp. 1399 - 1409
• Main Authors: le Roux, Carel W, Greenway, Frank, Lau, David C W, Van Gaal, Luc, Skjøth, Trine V, Manning, Linda Shapiro, Pi-Sunyer, Xavier, Linn, Thomas, Mölle, Andrea, Stübler, Petra, Tosch-Sisting, Regina, Pacini, Furio, Rotella, Carlo Maria, Buscemi, Silvio, Raya, Pedro Mezquita, Freijoo, Felipe Casanueva, de Barbará, Ramón Gomis, Farsang, Csaba, Zahorska-Markiewicz, Barbara, Pupek-Musialik, Danuta, Franek, Edward, Ostrowska, Lucyna, Olszanecka-Glinianowicz, Magdalena, Micic, Dragan, Ludvik, Bernhard, Paulweber, Bernhard, Prager, Rudolf, Savolainen, Markku, Krempf, Michel, Mira, Reginald, van Berkum, Frank, Hjelmesæth, Jøran, Kulseng, Bård, Golay, Alain, Sathyapalan, Thozhukat, Wilding, John, Wittert, Gary, Caterson, Ian, Prins, John, Neto, Bruno Geloneze, Gross, Jorge Luiz, de Almeida Suplicy, Henrique, Thacker, Hemant P, Chandalia, Hemaraj, Kalra, Sanjay, Deshpande, Neeta, Deshmukh, Vaishali Chetan, Maislos, Maximo, Nabriski, Dan, Karnieli, Eddy, Gonzalez-Galvez, Guillermo, del Rosario Arechavaleta-Granell, Maria, Franco, Guadalupe Morales, Suplotova, Lyudmila Aleksandrovna, Ruyatkina, Ludmila Aleksandrovna, Startseva, Maria A, Badat, Aysha, Guler, Serdar, Ulgen, Ender, Delibasi, Tuncay, Labonte, Isabelle, Lau, David, Liutkus, Joanne, O'Keefe, Dennis, Padwal, Raj, Ransom, Thomas P.P., Aqua, Keith, Aronoff, Stephen L, Blevins, Thomas Craig, Brockmyre, Andrew Peter, Chaykin, Louis B, Davis, Matthew G, Farrell, James, Finneran, Matthew Patrick, Forker, Alan, Geller, Steven Andrew, Gill, Santosh, Glaser, Linda, Herman, Lee, Hoekstra, John, Ingebretsen, Richard, Kaplan, Roy, Haase, Gregory A, Kerzner, Boris, Koltun, William, Krieger, Diane R, Lewis, Cora Elizabeth, Marple, Richard N, Mello, Curtis John, O'Neil, Patrick, Pi-Sunyer, F. Xavier, Pucillo, Ronald M, Rothman, Jeffrey, Sellers, Gladstone, Smith, Timothy, Soufer, Joseph, Schramm, Erich Lloyd, Berg, Saul Reuel, Wyatt, Holly Roxanna, Simon, James Alan
• Format: Journal Article Web Resource
• Language: English
• Published: England Elsevier Ltd 08.04.2017; Elsevier Limited; Elsevier; Lancet Publishing Group
• Subjects: Adult; Antidiabetics; Autoimmune diseases; Back pain; Blood Glucose; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Mass Index; Body Weight; Body Weight - drug effects; Body weight loss; Classification; Clinical medicine; Clinical trials; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Diagnosis; Double-Blind Method; Double-blind studies; Endocrinologie, métabolisme & nutrition; Endocrinology, metabolism & nutrition; Evaluation; Evidence-based medicine; Female; Food and Nutrition; Gallbladder diseases; Gastrointestinal surgery; GLP1R protein, human; Glucagon-Like Peptide 1; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - pharmacology; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-1 Receptor - administration & dosage; Glucagon-Like Peptide-1 Receptor Agonists; Glucose; Glucose metabolism; Health risks; Hemoglobin; Human health and pathology; Human health sciences; Humans; Hypertension; Hypoglycemic Agents; Hypoglycemic Agents - therapeutic use; Immunology; Incretins; Incretins - therapeutic use; Injections, Subcutaneous; Internal Medicine; Investigations; Life Sciences; Liraglutide; Liraglutide - administration & dosage; Liraglutide - adverse effects; Liraglutide - pharmacology; Male; Middle Aged; Nutrition research; Obesity; Obesity - complications; Obesity - drug therapy; Obesity - epidemiology; Pharmacie, pharmacologie & toxicologie; Pharmacy, pharmacology & toxicology; Physical activity; Placebos; Placebos - administration & dosage; Placebos - pharmacology; Prediabetic State; Prediabetic State - complications; Prediabetic State - diagnosis; Prediabetic State - prevention & control; Randomization; Risk management; Risk reduction; Risk Reduction Behavior; Sciences de la santé humaine; Treatment Outcome; Weight control; Weight Loss; Weight Loss - drug effects; Weight reduction; North America; Europe
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(17)30069-7

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. 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. 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. 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. Novo Nordisk, Denmark.