GLP-1 agonist lowers CV biomarkers in high-risk T2DM patients
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
Type 2 diabetic (T2DM) patients are at high CVD risk, particularly those with albuminuria . Liraglutide has glucose-lowering effects but also supports weight loss, lowers blood pressure (BP), albuminuria and lipid-levels. Moreover it is suggested that liraglutide may have anti-inflammatory and vasodilatory effects [2-4]. Endothelial dysfunction is an early marker of atherosclerosis, and inflammatory processes play an important role in atherosclerotic cardiovascular disease .
Therefore, it was hypothesised in current study that liraglutide treatment is associated with the reduction of inflammatory biomarkers and CV risk biomarkers in high-risk patients. To validate this, a randomised, double-blind, cross-over study was performed to evaluate the effect of liraglutide on five CVD-associated biomarkers in 27 T2DM patients with persistent albuminuria. For this, 12 weeks of treatment was followed by a 4-week washout period.
The biomarkers reflect different pathophysiology and included tumour necrosis factor-alpha (TNF-alpha), soluble urokinase plasminogen-activator-receptor (suPAR), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), and copeptin.
- LDL-C was 0.21 mmol/L (95% CI: 0.03-0.40) lower after liraglutide treatment compared to placebo (P=0.028), total cholesterol was 0.30 mmol/L lower (95% CI: 0.02-0.58, P=0.034) and there was no significant effect on triglycerides or HDL-C.
- TNF-alpha was 12% (95% CI: 3-20) lower after liraglutide treatment compared to placebo (P=0.012). In univariate and multivariate models, no associations between change in TNF-alpha and change in HbA1c, weight, 24-hour systolic BP (SBP), urinary albumin excretion rate (UAER), 24-hour heart rate (HR), LDL-C or total cholesterol were observed (P≥0.064).
- No differences were observed when comparing plasma or urinary suPAR at the end of liraglutide treatment to end of placebo (plasma P=0.61 and urinary P=0.49).
- MR-proADM was 4% (95% CI: 0-8) lower after liraglutide treatment compared to placebo (P=0.038).
- In univariate models, change in MR-proADM was associated with change in weight (P=0.022, R2=0.18) but not with HbA1c, 24-hour SBP, UAER, 24-hour HR, LDL-C or total cholesterol.
- MR-proANP was 13% (95% CI: 4-21) lower after liraglutide treatment compared to placebo (P=0.006).
- In univariate models, reduction in MR-proANP was associated with an increased 24-hour HR (P<0.001; R2=0.53), but not with change in HbA1c, 24-hour SBP, UAER or weight (P≥0.38).
- No significant differences were observed when comparing copeptin or norepinephrine at the end of liraglutide treatment to end of placebo (P=0.75 and P=0.58, respectively).
In T2DM patients with albuminuria, liraglutide treatment was associated with reductions in circulating levels of CV risk biomarkers TNF-alpha, MR-proADM and MR-proANP. These findings support the hypothesis that liraglutide treatment may be associated with the reduction of inflammatory and CV risk biomarkers in high-risk patients.