Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

Abstract

Background Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with 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. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment. Methods Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels. Results Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (− 9%, beta = − 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment. Conclusions Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement. Trial registration Eudract: 2013-001356-36

Liraglutide and not lifestyle intervention reduces soluble CD163 after comparable weight loss in obese participants with prediabetes or type 2 diabetes mellitus

“…Clinical and biochemical baseline characteristics of the study subjects have been previously presented [ 12 , 13 , 16 ] and relevant variables are shown in Table 1 . Patients randomized to liraglutide treatment and lifestyle intervention were similar on most parameters, except for triglycerides (TG), waist circumference and visceral adipose tissue (VAT) being higher in the liraglutide arm.…”

“…In clinical trials, liraglutide reduces levels of various inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-6 in overweight and obese individuals with T2DM [ 9 – 11 ]. We have previously shown that the inflammatory marker soluble suppression of tumorigenesis-2 (sST2) was decreased after weight loss induced by liraglutide treatment, but not after comparable weight loss due to lifestyle changes [ 12 ]. Interestingly, in the same cohort, liraglutide achieved a more pronounced reduction in visceral adipose tissue (VAT) and improvement in beta cell function, independently of weight loss [ 13 ].…”

Liraglutide improves adipose tissue remodeling and mitochondrial dynamics in a visceral obesity model induced by a high-fat diet

“…Regarding the effects of LGT, it has been reported that it would reduce Gal-3 levels in the liver of an obese animal model ( Tølbøl et al, 2018 ). However, Simeone et al (2022) recently reported that LGT treatment did not affect circulating Gal-3 levels in obese patients. In accordance, we did not observe changes in Gal-3 expression in VAT in response to LGT administration.…”

Development of a core outcome set for cardiovascular diabetology: a methodological framework

“…The objective of clinical research in the field is to help manage diabetes, promote cardiovascular health, reduce cardiovascular adverse events, and improve the long-term prognosis ( 9 – 13 ). The research mainly involves drug treatment and management ( 12 ), lifestyle intervention ( 14 ), and other aspects.…”

“…When developing a COS, we should follow the COS-STAR guidelines ( 28 ), the COS-STAP guidelines, and the handbook for developing COS. As the outcomes in cardiovascular diabetology are complex ( 12 – 14 ), potential modification of the steps will be performed based on the characteristics of cardiovascular diabetology in order to develop a high-quality COS. In the current paper, we report the methodological framework and hope it will help other researchers in this field.…”