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

Diabetes Obes Metab. 2017 Jun;19(6):901-905. doi: 10.1111/dom.12884. Epub 2017 Mar 2.

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.

Keywords: GLP-1 analogue; clinical trial; liraglutide.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / blood
  • Adrenomedullin / drug effects
  • Aged
  • Albuminuria / blood*
  • Albuminuria / drug therapy
  • Albuminuria / etiology
  • Atrial Natriuretic Factor / blood
  • Atrial Natriuretic Factor / drug effects
  • Biomarkers / blood
  • Cardiovascular Diseases / etiology*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Double-Blind Method
  • Female
  • Glycopeptides / blood
  • Glycopeptides / drug effects
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Liraglutide / therapeutic use*
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptide Fragments / drug effects
  • Protein Precursors / blood
  • Protein Precursors / drug effects
  • Receptors, Urokinase Plasminogen Activator / blood
  • Receptors, Urokinase Plasminogen Activator / drug effects
  • Risk Factors
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / drug effects

Substances

  • Biomarkers
  • Glycopeptides
  • Hypoglycemic Agents
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Urokinase Plasminogen Activator
  • Tumor Necrosis Factor-alpha
  • copeptins
  • mid-regional pro-adrenomedullin, human
  • midregional pro-atrial natriuretic peptide, human
  • Adrenomedullin
  • Liraglutide
  • Atrial Natriuretic Factor