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

Osteoarthritis and cartilage open Pub Date : 2025-01-03 DOI:10.1016/j.ocarto.2024.100562

Asbjørn Seenithamby Poulsen , Zara Rebecca Stisen , Marie Skougaard , Robin Christensen , Anders Overgaard , Henrik Gudbergsen , Stine Jacobsen , Andreas Peter Balslev-Clausen , Marius Henriksen , Lars Erik Kristensen , Henning Bliddal

{"title":"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","authors":"Asbjørn Seenithamby Poulsen , Zara Rebecca Stisen , Marie Skougaard , Robin Christensen , Anders Overgaard , Henrik Gudbergsen , Stine Jacobsen , Andreas Peter Balslev-Clausen , Marius Henriksen , Lars Erik Kristensen , Henning Bliddal","doi":"10.1016/j.ocarto.2024.100562","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>A secondary analysis of a randomized, double-blinded, placebo-controlled trial in adults with overweight (BMI≥27 kg/m<sup>2</sup>) 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.</div></div><div><h3>Results</h3><div>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, <em>P</em> = 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, <em>P</em> = 0.78).</div></div><div><h3>Conclusion</h3><div>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.</div></div><div><h3>Trial registration</h3><div>Clinicaltrials.gov: <span><span>NCT02905864</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100562"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773487/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Osteoarthritis and cartilage open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2665913124001298","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

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.