Liraglutide effects on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub-analysis of a randomised, placebo-controlled, double-blind, cross-over trial

We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: 1) Tumour necrosis factor-alpha (TNF-alpha); 2) Soluble urokinase plasminogen activator receptor (suPAR); 3) Mid-regional pro-adrenomedullin (MR-proADM); 4) Mid-regional pro-atrial natriuretic peptide (MR-proANP); and 5) Copeptin, in type 2 diabetes patients with albuminuria. In a randomised, double-blind, placebo-controlled, cross-over trial we enrolled patients 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/1.73m(2) . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in random order. Primary endpoint was change in albuminuria; this is a prespecified sub-study. Thirty-two patients were randomised, 27 completed the study. TNF-alpha was 12 (95% CI: 3;20)% lower after liraglutide treatment compared to placebo (p = 0.012); MR-proADM was 4 (95% CI: 0;8)% lower after liraglutide treatment compared to placebo (p = 0.038); and MR-proANP was 13 (95% CI: 4;21)% lower after liraglutide treatment compared to placebo (p = 0.006). We demonstrated anti-inflammatory effects of liraglutide treatment, reflected by reductions in levels of TNF-alpha and MR-proADM, while reduction in MR-proANP may reflect clinically relevant benefit in heart failure.

CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov, NCT02545738.