Effect of weight loss and liraglutide on neutrophil gelatinase-associated lipocalin levels among individuals with overweight and knee osteoarthritis: Exploratory analyses of a randomized controlled trial

Objective: Obesity is a major risk factor for osteoarthritis (OA). Adipose tissues may be linked to OA development through secretion of potential proinflammatory cytokines including neutrophil gelatinase-associated lipocalin (NGAL). Our objective was to assess changes in serum NGAL after a low-calorie diet (LCD) and subsequent glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment. Design: A secondary analysis of a randomized, double-blinded, placebo-controlled trial in adults with overweight (BMI≥27 ​kg/m²) and symptomatic, early-to-moderate radiographic knee OA. Prior to randomization, participants underwent an 8-week LCD (week −8 to 0). Participants who lost min. 5 ​% of initial bodyweight were randomized 1:1 to liraglutide 3 ​mg/d or placebo for 52 weeks. Main outcome was change in serum NGAL from enrollment (week −8) to randomization (week 0). Other outcome was change in serum NGAL from week 0 to week 52 comparing liraglutide and placebo. Results: 168 participants were enrolled to the initial intensive diet intervention; 127 participants, with NGAL samples, were randomized. Following the 8-week diet intervention, NGAL concentrations rose by 93.0 ​ng/mL (95 ​% CI: 18.9 to 167.1, P ​= ​0.015), with no correlation to weight loss magnitude. 52 weeks of treatment with either liraglutide or placebo, liraglutide did not cause a greater decrease in serum NGAL (14.9 ​ng/ml, 95%CI: −92.1 to 121.7 ​ng/mL, P ​= ​0.78). Conclusion: An intensive 8-week calorie restriction was associated with a rise in serum NGAL. Compared to placebo, 52 weeks of liraglutide did not cause additional changes in NGAL. This indicates a complex pattern of proinflammatory cytokine-release during hypocaloric diet interventions. Trial registration: Clinicaltrials.gov: NCT02905864.