Liraglutide suppresses non-esterified free fatty acids and soluble vascular cell adhesion molecule-1 compared with metformin in patients with recent-onset type 2 diabetes

Abstract

BackgroundIt has been suggested that liraglutide could have an impact on glucose and lipid metabolism disorder and adhesion molecule activation, which may play important roles in the vascular damage of diabetes. In this study, we examined the effects of liraglutide versus metformin on non-esterified free fatty acids, beta-cell insulin secretion, and adhesion molecule levels in patients with recent-onset type 2 diabetes mellitus.MethodsIn this study, 60 patients newly diagnosed with type 2 diabetes mellitus (mean age 33.97 ± 5.67 years) were randomly assigned to receive once-daily subcutaneous liraglutide or oral metformin. Before the study and after the 8-week treatment period, a 75 g oral glucose tolerance test was performed. Plasma glucose, lipids and lipoprotein, plasma insulin, glycaemic and insulin responses, non-esterified free fatty acids (NEFA), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were evaluated.ResultsAfter 8 weeks, 120 min of NEFA (155 ± 125 vs 99 ± 73 µmol/L, P = 0.026) and the levels of sVCAM-1 (465 ± 136 vs 382 ± 131 ng/ml, P = 0.013) significantly decreased, while the early phase insulin secretion index (24.94 [7.78, 38.89] vs. 31.13 [17.67, 59.09], P = 0.031), fasting plasma insulin (104 [51, 123] vs 113 [54, 171] mIU/L, P = 0.015), 60 min plasma insulin (326 [165, 441] vs 471 [334, 717] mIU/L, P = 0.005), 120 min plasma insulin (401 [193, 560] vs 500 [367, 960] mIU/L, P = 0.047), and insulin area under the curve (AUCins) (648 [321, 742] vs 738 [451, 1118] mIU/L, P = 0.005) remarkably increased for patients in the liraglutide treatment group. The levels of sVCAM-1 dramatically decreased after 8 weeks of liraglutide treatment (503 ± 182 vs 382 ± 131 ng/ml, P = 0.046) compared to that of the metformin treatment group. At the same time, the differences before and after liraglutide treatment in 120 min of NEFA (− 32 [− 96, − 5] vs 5 [− 35, 38] µmol/L, P = 0.033) and AUCins (738 [451, 1118] vs 594 [357, 1216] mIU/L, P = 0.014) were remarkably enhanced compared to that of the metformin therapy. Nevertheless, there were no significant differences in fasting NEFA after liraglutide or metformin treatment. The reduction of 120 min NEFA (ΔNEFA) was positively correlated with the decrease of sVCAM-1 (ΔsVCAM-1) after 8 weeks of liraglutide treatment (r = 0.523, P = 0.003).ConclusionsOur results demonstrate that liraglutide administration is more effective than metformin in reducing 120 min NEFA and suppressing sVCAM-1 levels for recent-onset type 2 diabetes mellitus. We suggest that this outcome may be because liraglutide is associated with potentiating insulin secretion capacity, inhibiting vascular inflammatory cytokines, and antagonizing atherosclerosis.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0701-4) contains supplementary material, which is available to authorized users.

Liraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet

“…Further, db/db mice fed with high fat diet improved hepatic lipid accumulation by promoting reversal of cholesterol transport [40]. In our model of metabolic syndrome, Vcam-1 mRNA expression showed a strong trend to be reduced by LIRA in the kidney [21] but not in the myocardium [13]. On the other hand, markers of macrophage infiltration (CD68 protein expression and CD+ cell density in sections) suggest that LIRA greatly suppressed macrophage infiltration in both the heart and kidney in our studies.…”

“…LIRA treatment shown greater reductions in HbA1c in patients with cardiovascular events compared with placebo [12]. In addition, LIRA administration was more effective than metformin in suppressing vascular cell adhesion molecule (VCAM)-1 levels and reducing non-esterified free fatty acids recent-onset T2DM [13]. Indeed, previous studies have reported that GLP-1 agonist treatment has anti-inflammatory effects on peripheral vascular endothelial cells by increasing NO production and inhibiting cellular oxidative stress and apoptosis in diabetic animal models [14][15][16].…”

Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis

“…Reduction in arterial stiffness, LV myocardial strain, twisting and untwisting, N-terminal pro-brain natriuretic peptide, and oxidative stress with liraglutide could offer myocardial protection and prevention of diabetic heart disease [55]. Moreover, liraglutide reduces postprandial non-esterified free fatty acids and suppresses soluble vascular cell adhesion molecule-1 compared to metformin [56]. It protects against acute liver injury in the mouse [57].…”

Liraglutide ameliorates beta-cell function, alleviates oxidative stress and inhibits low grade inflammation in young patients with new-onset type 2 diabetes

“…We demonstrated in this study that liraglutide and metformin treatment significantly reduced the expression of urinary 8-OH-DG and 8-iso-PGF 2α .than those of baseline. At the same time, we also demonstrated that liraglutide treatment inhibited the expression of sVCAM-1 and hs-CRP [25]. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), produced by oxidation of the nucleoside deoxyguanosine and subsequently excreted directly into urine, has been considered as a sensitive marker for oxidative DNA damage [26].…”