Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Studies and Practice

Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: The SCALE Maintenance randomized study

International Journal of Obesity volume 37, pages 1443–1451 (2013)Cite this article

Subjects

An Erratum to this article was published on 14 October 2014

An Erratum to this article was published on 03 September 2013

This article has been updated

Abstract

Objective:

Liraglutide, a once-daily human glucagon-like peptide-1 analog, induced clinically meaningful weight loss in a phase 2 study in obese individuals without diabetes. The present randomized phase 3 trial assessed the efficacy of liraglutide in maintaining weight loss achieved with a low-calorie diet (LCD).

Methods:

Obese/overweight participants (⩾18 years, body mass index ⩾30 kg m−2 or ⩾27 kg m−2 with comorbidities) who lost ⩾5% of initial weight during a LCD run-in were randomly assigned to liraglutide 3.0 mg per day or placebo (subcutaneous administration) for 56 weeks. Diet and exercise counseling were provided throughout the trial. Co-primary end points were percentage weight change from randomization, the proportion of participants that maintained the initial ⩾5% weight loss, and the proportion that lost ⩾5% of randomization weight (intention-to-treat analysis). ClinicalTrials.gov identifier: NCT00781937.

Results:

Participants (n=422) lost a mean 6.0% (s.d. 0.9) of screening weight during run-in. From randomization to week 56, weight decreased an additional mean 6.2% (s.d. 7.3) with liraglutide and 0.2% (s.d. 7.0) with placebo (estimated difference −6.1% (95% class intervals −7.5 to −4.6), P<0.0001). More participants receiving liraglutide (81.4%) maintained the ⩾5% run-in weight loss, compared with those receiving placebo (48.9%) (estimated odds ratio 4.8 (3.0; 7.7), P<0.0001), and 50.5% versus 21.8% of participants lost ⩾5% of randomization weight (estimated odds ratio 3.9 (2.4; 6.1), P<0.0001). Liraglutide produced small but statistically significant improvements in several cardiometabolic risk factors compared with placebo. Gastrointestinal (GI) disorders were reported more frequently with liraglutide than placebo, but most events were transient, and mild or moderate in severity.

Conclusion:

Liraglutide, with diet and exercise, maintained weight loss achieved by caloric restriction and induced further weight loss over 56 weeks. Improvements in some cardiovascular disease-risk factors were also observed. Liraglutide, prescribed as 3.0 mg per day, holds promise for improving the maintenance of lost weight.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

Change history

  • 12 November 2013

    This article has been corrected since online publication and an erratum is also printed in this issue

References

  1. World Health Organization. Obesity: preventing and managing the global epidemic. Geneva, Switzerland: World Health Organization, 1998.

  2. National Institutes of Health. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. Obes Res 1998; 6 (Suppl 2): 51S–209S.

    Google Scholar 

  3. Diabetes Prevention Program (DPP) Research Group. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care 2002; 25: 2165–2171.

    Article  Google Scholar 

  4. Wadden TA, Webb VL, Moran CH, Bailer BA . Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation 2012; 125: 1157–1170.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wing RR, Jeffery RW, Hellerstedt WL . A prospective study of effects of weight cycling on cardiovascular risk factors. Arch Intern Med 1995; 155: 1416–1422.

    Article  CAS  PubMed  Google Scholar 

  6. Wing RR, Tate DF, Gorin AA, Raynor HA, Fava JL . A self-regulation program for maintenance of weight loss. N Engl J Med 2006; 355: 1563–1571.

    Article  CAS  PubMed  Google Scholar 

  7. Svetkey LP, Stevens VJ, Brantley PJ, Appel LJ, Hollis JF, Loria CM et al. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA 2008; 299: 1139–1148.

    Article  CAS  PubMed  Google Scholar 

  8. Wadden TA, Neiberg RH, Wing RR, Clark JM, Delahanty LM, Hill JO et al. Four-year weight losses in the Look AHEAD study: factors associated with long-term success. Obesity 2011; 19: 1987–1998.

    Article  PubMed  Google Scholar 

  9. Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): A randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012; 95: 297–308.

    Article  CAS  PubMed  Google Scholar 

  10. Sjostrom L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HPF et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 1998; 352: 167–173.

    Article  CAS  PubMed  Google Scholar 

  11. Davidson MH, Hauptman J, Digirolamo M, Foreyt JP, Halsted CH, Heber D et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: A randomized controlled trial. JAMA 1999; 281: 235–242.

    Article  CAS  PubMed  Google Scholar 

  12. Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F, Leutenegger E . Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. Am J Med 1999; 106: 179–184.

    Article  CAS  PubMed  Google Scholar 

  13. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363: 245–256.

    Article  CAS  PubMed  Google Scholar 

  14. Blonde L, Russell-Jones D . The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies. Diabetes Obes Metab 2009; 11 (Suppl 3): 26–34.

    Article  CAS  PubMed  Google Scholar 

  15. Summary of product characteristics, Victoza 2012, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001026/WC500050017.pdf Accessed 14 Nov 2012.

  16. Astrup A, Rossner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009; 374: 1606–1616.

    Article  CAS  PubMed  Google Scholar 

  17. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes 2012; 36: 843–854.

    Article  CAS  Google Scholar 

  18. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2000; 284: 3043–3045.

    Article  PubMed  Google Scholar 

  19. International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. Good Clinical Practice. 1-May- 1996, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1_Guideline.pdf Accessed 14 Nov 2012.

  20. Mundt JC, Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Modell JG et al. Feasibility and validation of a computer-automated Columbia-Suicide severity rating scale using interactive voice response technology. J Psychiatr Res 2010; 44: 1224–1228.

    Article  PubMed  Google Scholar 

  21. Kroenke K, Spitzer RL, Williams JB . The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16: 606–613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Corsetti JP, Cox C, Schulz TJ, Arvan DA . Combined serum amylase and lipase determinations for diagnosis of suspected acute pancreatitis. Clin Chem 1993; 39: 2495–2499.

    CAS  PubMed  Google Scholar 

  23. Astrup A, Caterson I, Zelissen P, Guy-Grand B, Carruba M, Levy B et al. Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects. Obes Res 2004; 12: 1658–1669.

    Article  CAS  PubMed  Google Scholar 

  24. Food and Drug Administration. FDA Guidance for Industry: Developing products for weight management, 2007, http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071612.pdf Accessed 14 Nov 2012.

  25. Hill JO, Hauptman J, Anderson JW, Fujioka K, O'Neil PM, Smith DK et al. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: A 1-y study. Am J Clin Nutr 1999; 69: 1108–1116.

    Article  CAS  PubMed  Google Scholar 

  26. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005; 353: 2111–2120.

    Article  CAS  PubMed  Google Scholar 

  27. Wirth A, Krause J . Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 2001; 286: 1331–1339.

    Article  CAS  PubMed  Google Scholar 

  28. Munro JF, MacCusih AC, Wilson EM, Duncan LJ . Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1968; 1: 352–354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wadden TA, Anderson DA, Foster GD . Two-year changes in lipids and lipoproteins associated with the maintenance of a 5 to 10% reduction in initial weight: some findings and some questions. Obes Res 1999; 7: 170–178.

    Article  CAS  PubMed  Google Scholar 

  30. Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons M . Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993; 77: 1287–1293.

    CAS  PubMed  Google Scholar 

  31. Marso SP, Lindsey JB, Stolker JM, House JA, Martinez RG, Kennedy KF et al. Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies. Diab Vasc Dis Res 2011; 8: 237–240.

    Article  PubMed  Google Scholar 

  32. NCEP report. Implications of recent clinical trials for the national cholesterol education program Adult Treatment Panel III guidelines Endorsed by the National Heart, Lung, and Blood Institute, American College of Cardiology Foundation, and American Heart Association. Circulation 2004; 110: 227–239.

    Article  Google Scholar 

  33. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C . Definition of Metabolic Syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation 2004; 109: 433–438.

    Article  PubMed  Google Scholar 

  34. The Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute. JAMA 2003; 289: 2560–2572.

Download references

Acknowledgements

We thank the study participants and acknowledge the members of the NN8022-1923 study group, their staff and clinical trial personnel, without whom this trial would not have been possible. We also thank Angela Harper, (Novo Nordisk A/S, Denmark), Edward S Kimball, (Novo Nordisk, Inc., USA), and Caroline Moran (University of Pennsylvania) for editorial and writing assistance. Liraglutide is a Novo Nordisk proprietary compound under development for chronic weight management. This work was funded by Novo Nordisk A/S, Denmark.

Author information

Author notes

  1. T A Wadden, P Hollander, S Klein, K Niswender, V Woo, P M Hale and L Aronne: See appendix for Listed NN8022-1923 Investigators.

Authors and Affiliations

  1. Center for Weight and Eating Disorders, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    T A Wadden

  2. Diabetes and Endocrine Center, Dallas, TX, USA

    P Hollander

  3. Washington University School of Medicine, St Louis, MO, USA

    S Klein

  4. Vanderbilt University School of Medicine, Nashville, TN, USA

    K Niswender

  5. Health Sciences Center, University of Manitoba, Winnipeg, MB, Canada

    V Woo

  6. Novo Nordisk Inc., Princeton, NJ, USA

    P M Hale

  7. Weill-Cornell Medical Center, New York, NY, USA

    L Aronne

Authors
  1. T A Wadden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Hollander
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Niswender
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P M Hale
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L Aronne
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the NN8022-1923 Investigators

Corresponding author

Correspondence to T A Wadden.

Ethics declarations

Competing interests

PMH is an employee of Novo Nordisk, and also owns stock in the company. TAW serves on advisory boards for Novo Nordisk and Orexigen Pharmaceuticals. PH serves on an advisory board and is a consultant for Novo Nordisk. SK is a consultant for Takeda Pharmaceuticals and Vivus. KN is a consultant for Novo Nordisk and has done commercially sponsored research for Novo Nordisk. VW serves on advisory boards, has held paid lectures or has done commercially sponsored research for Novo Nordisk, Eli Lilly, Sanofi, Bristol-Myers Squibb, AstraZeneca and Boehringer Ingelheim. LA is a consultant or receives research support from Amylin Pharmaceuticals, F Hoffman-La Roche, Abbott Laboratories, Ethicon Endo-Surgery, Orexigen Therapeutics, Vivus, GlaxoSmithKline Consumer Healthcare, LP, Takeda Pharmaceuticals and Zafgen. He has ownership interest in Cardiometabolic Support Network, LLC and Atlas Therapeutics.

Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

Supplementary information

Appendix

Appendix

NN8022-1923 Investigators

USA: Cory Anderson, Louis Aronne, Harold Bays, David C Bird, Thomas Blevins, Victor Elinoff, Kevin Furlong, William Gonte, Priscilla Hollander, Ronald Hsieh, Dean Karras, Robert Kaufmann, Samuel Klein, Thomas Littlejohn, Barry Lubin, Kevin Niswender, Robert Orr, John Pullman, Andrea Ramsay, Paul Rosenblit, Cynthia Strout, Mark Turner, Jeffrey Unger, Thomas Wadden, Bret Wittmer and Temala Zimmerman.

Canada: Vincent Woo, Joseph Berlingieri, Guy Tellier, Martyn Chilvers, Gordon Schacter, Andre Belanger, Pierre Martin, Jean Sebastien Gauthier and Sean Wharton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wadden, T., Hollander, P., Klein, S. et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: The SCALE Maintenance randomized study. Int J Obes 37, 1443–1451 (2013). https://doi.org/10.1038/ijo.2013.120

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2013.120

Keywords

This article is cited by

Search

Advanced search

Quick links