title: Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub-analysis of a randomized, placebo-controlled, double-blind, crossover trial.
abstract: We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: tumour necrosis factor (TNF)-α; soluble urokinase plasminogen activator receptor (suPAR); mid-regional pro-adrenomedullin (MR-proADM); mid-regional pro-atrial natriuretic peptide (MR-proANP); and copeptin, in people with type 2 diabetes with albuminuria. In a randomized, double-blind, placebo-controlled, crossover trial we enrolled people with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio [UACR] >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. Participants received liraglutide (1.8 mg/d) and matched placebo for 12 weeks, in random order. The primary endpoint was change in albuminuria; this was a prespecified sub-study. A total of 32 participants were randomized, of whom 27 completed the study. TNF-α level was 12% (95% confidence interval [CI] 3; 20) lower after liraglutide treatment compared with placebo (P = .012); MR-proADM level was 4% (95% CI 0; 8) lower after liraglutide treatment compared with placebo (P = .038), and MR-proANP level was 13% (95% CI 4; 21) lower after liraglutide treatment compared with placebo (P = .006). In the present study, we showed anti-inflammatory effects of liraglutide treatment, reflected in reductions in levels of TNF-α and MR-proADM, while the reduction in MR-proANP levels may represent a clinically relevant benefit with regard to heart failure.
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
authors.forename: Bernt Johan
authors.identifier: 0000-0002-1489-0636
authors.initials: BJ
authors.lastname: von Scholten
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Rosenlund
authors.affiliation: Department of Clinical Biochemistry, Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Eugen-Olsen
authors.affiliation: Nutopi Sp. z o.o., Poznan, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Pielak
authors.affiliation: Department of Endocrinology, Herlev Hospital, Herlev, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
authors.forename: Tine W
authors.initials: TW
authors.lastname: Hansen
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.|Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D053607:Adrenomedullin / Q000097:blood / Q000187:drug effects; D000368:Aged; D000419:Albuminuria / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006020:Glycopeptides / Q000097:blood / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D011498:Protein Precursors / Q000097:blood / Q000187:drug effects; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood / Q000187:drug effects; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D011498:Protein Precursors; D055293:Receptors, Urokinase Plasminogen Activator; D014409:Tumor Necrosis Factor-alpha; C048197:copeptins; C574167:mid-regional pro-adrenomedullin, human; C552580:midregional pro-atrial natriuretic peptide, human; D053607:Adrenomedullin; D000069450:Liraglutide; D009320:Atrial Natriuretic Factor
keywords: GLP-1 analogue; clinical trial; liraglutide