Article Text

Download PDFPDF

  1. Henrik Gudbergsen1,
  2. Anders Overgaard1,
  3. Marius Henriksen1,2,
  4. Eva Ejlersen Wæhrens1,3,
  5. Henning Bliddal1,
  6. Robin Christensen1,4,
  7. Sabrina Mai Nielsen1,
  8. Mikael Boesen1,5,
  9. Filip Krag Knop6,7,
  10. Arne Astrup8,
  11. Marianne Uggen Rasmussen1,
  12. Cecilie Rødgaard Bartholdy1,
  13. Cecilie Daugaard1,
  14. Else Marie Bartels1,
  15. Karen Ellegaard1,
  16. Berit Lilienthal Heitmann1,9,
  17. Lars Erik Kristensen1
  1. 1Bispebjerg-Frederiksberg Hospital, University of Copenhagen, The Parker Institute, Frederiksberg, Denmark
  2. 2Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Department of Physio- and Occupational Therapy, Frederiksberg, Denmark
  3. 3Research Unit for General Practice, Institute of Public Health, University of Southern Denmark, Research Initiative for Activity Studies and Occupational Therapy, Odense, Denmark
  4. 4Odense University Hospital, Department of Rheumatology, Odense, Denmark
  5. 5Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Department of Radiology, Frederiksberg, Denmark
  6. 6Steno Diabetes Center Copenhagen, Gentofte Hospital, Clinical Metabolic Physiology, Hellerup, Denmark
  7. 7Faculty of Health and Medical Sciences, University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark
  8. 8Faculty of Science, University of Copenhagen, Department of Nutrition, Exercise and Sports, Copenhagen, Denmark
  9. 9Section for General Medicine, University of Copenhagen, Department of Public Health, Copenhagen, Denmark


Background Weight loss is recommended as treatment of concomitant knee osteoarthritis (OA) and overweight. The GLP-1 receptor agonist liraglutide has been shown effective in maintaining or even further reducing weight loss, but the compound has not been tested in a population of patients with overweight and knee OA.

Objectives The objective of this trial was to investigate if liraglutide in a 3 mg/day dosage was effective in maintaining weight loss and symptomatic effects 52 weeks after an initial 8-week dietary-based weight loss intervention dosing in patients with overweight and knee OA.

Methods Patients with overweight or obesity and knee OA participated in a randomised, double blind, placebo-controlled, parallel group, single-centre trial. Patients were provided an initial 8-week run-in diet intervention (week -8 to 0) including a low-calorie diet from Cambridge Weight Plan and dietetic counselling. At week 0 patients who had lost at least 5% of their initial body weight were randomised to liraglutide 3 mg/day or placebo for 52 weeks. The co-primary outcomes were changes in body weight and the KOOS pain subscale from week 0 to 52. Trial registration: NCT02905864. Analyses were based on the intention-to-treat population.

Results 168 patients (Kellgren-Lawrence grade 1-3) were enrolled in the initial 8-week diet intervention and 156 patients were randomised (Figure 1). Before randomisation the 156 patients had lost 12.46 kg (SD:3.82) (≈12%) and improved in KOOS pain corresponding to 11.86 points (SD:15.13) (≈19%). Baseline characteristics were similar in the intervention and control groups. From baseline to 52 weeks there was a statistically and clinically significant difference in the weight loss between the liraglutide and the placebo groups (mean -2.76 and 1.17 kg, respectively; group difference, 3.93 kg; 95%CI -6.85 to -1.02; p=0.008), there was no difference between groups in change in KOOS pain (mean changes: 0.35 and -0.55 points, respectively; group difference, 0.89 points; 95%CI -3.89 to 5.68; p=0.713). Week 52 least squares means for body weight and KOOS pain showed similar results (Figure 2). 4 patients in the intervention and 4 patients in the control groups experienced serious adverse events, and no deaths were observed.

Conclusion In overweight patients with knee OA, an 8-week low-calorie diet intervention significantly reduced body weight and knee pain. Liraglutide treatment added after the initial diet-induced weight loss provided further weight loss over 1 year but did not reduce knee pain any further compared to placebo.

Disclosure of Interests henrik gudbergsen Grant/research support from: From Novo Nordisk, Employee of: Novo Nordisk, Speakers bureau: Pfizer, Anders Overgaard: None declared, Marius Henriksen Consultant for: Advisory board member for Thuasne Group, Eva Ejlersen Wæhrens: None declared, Henning Bliddal Grant/research support from: AbbVie. Oak Foundation, Robin Christensen Grant/research support from: AbbVie Inc, and the Oak Foundation, Speakers bureau: Roche, Sabrina Mai Nielsen: None declared, Mikael Boesen Shareholder of: Image Analysis Group, UK, Grant/research support from: Image Analysis Group, Oak Foundation, EUROSTARS, Consultant for: Esaote, Eli Lilly, Celgene, Carestream, UCB, Abbvie, Pfizer, Astra Zeneca, Roche, Siemens, Image Analysis Group, Speakers bureau: Carestream, Eli Lilly, Esaote, Abbvie, UCB, Pfizer, Image Analysis Group, Filip Krag Knop Grant/research support from: AstraZeneca, Gubra, Novo Nordisk, Sanofi and Zealand Pharma, Consultant for: Amgen, AstraZeneca, Eli Lilly, Novo Nordisk, Sanofi and Zealand Pharma, Speakers bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi and Zealand Pharma, Arne Astrup Grant/research support from: AA is currently involved in projects conducted by research groups at Department of Nutrition, Exercise and Sport, Faculty of Science, University of Copenhagen, funded by grants from Novo Nordisk DK, & Saniona, DK, Consultant for: AA is member of scientific advisory boards for BioCare Copenhagen & Novo Nordisk DK. He acts as consultant for Acino, Switzerland & Saniona DK., Marianne Uggen Rasmussen: None declared, Cecilie Rødgaard Bartholdy: None declared, Cecilie Daugaard: None declared, Else Marie Bartels: None declared, Karen Ellegaard: None declared, Berit Lilienthal Heitmann: None declared, Lars Erik Kristensen Grant/research support from: UCB, Biogen, Janssen Pharmaceuticals, and Novartis, Consultant for: Consultant for AbbVie, Amgen, Biogen, BMS, Celgene, Eli Lilly, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB Pharma., Speakers bureau: Pfizer, AbbVie, Amgen, UCB, BMS, Biogen, MSD, Novartis, Eli Lilly and Company, and Janssen Pharmaceuticals

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.