Background: Soluble suppression of tumorigenesis-2 (sST2) and Galectin-3 (Gal-3) have been associated with the pathogenesis of atherosclerosis and thrombosis.Their increased levels have a predictive role for  the risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk.

Aims: The aim of this work is to assess whether liraglutide treatment may modulate sST2 and Gal-3 levels  in patients with prediabetes or early T2DM independently of weight loss.

Methods: Forty metformin-treated obese subjects (BMI≥30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n=24)] or newly diagnosed T2DM (n=16), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Sixteen subjects were used as controls.  sST2 and Gal-3 were analyzed by ELISA. Thromboxane (TX)-dependent platelet activation as reflected in vivo by the urinary excretion of 11-dehydro-TXB₂ was measured by radioimmunoassay method.

Results: sST2 levels were comparable between controls and patients with prediabetes (p=0.988) or T2DM (p=0.179) (Fig.1A). Gal-3 levels were significantly higher in patients with IGT/IFG and T2DM as compared to controls (p<0.001 for both) (Fig.1B). Baseline sST2 plasma levels correlated directly with fasting insulin (Rho=0.391, p=0.014), total cholesterol (Rho=0.372, p=0.020), VAT (Rho=0.376, p=0.018) and HOMA-B (Rho=0.435 p=0.006). Baseline Gal-3 plasma levels correlated inversely with waist to hip ratio (WHR) (Rho=-0.455, p=0.004) and haemoglobin (Rho=-0.328, p=0.041) and directly with IL-6 (Rho=0.402, p=0.023). After weight loss, changes in sST2 correlated directly with changes in 11-dehydro-TXB₂ (Rho=0.346, p=0.033). sST2 levels  were significantly reduced only in the liraglutide arm (p=0.040) (Fig.2) while Gal-3 levels were not affected by weight loss in either arm.
Figure 1: basal levels of sST2 (A) and Gal-3 (B) in controls, patients with IGT/IFG and T2DMFigure 2. Changes in sST2 levels after liraglutide- or lifestyle-induced weight loss, in obese subjects with prediabetes and early type 2 diabetes. P values (lifestyle vs. liraglutide) are for comparison of changes between groups. 

Conclusions: Liraglutide-induced sST2 reduction suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on atherosclerosis and thrombosis.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/effects-of-liraglutide-vs-lifestyle-changes-on-sst2-and-galectin-3-in-obese-subjects-with-prediabetes-or-type-2-diabetes-after-comparable-weight-loss/