Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study

Abstract

BackgroundLiraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM.MethodsWe performed an 18-month prospective, real-world study. All subjects had T2DM and the MetS based on the AHA/NHLBI criteria. Subjects with a history of a major CV event were excluded. One hundred-twenty-one subjects (71 men and 50 women; mean age: 62 ± 9 years) with T2DM and the MetS, who were naïve to incretin-based therapies and treated with metformin only, were included. Liraglutide (1.2 mg/day) was added to metformin (1500–3000 mg/day) for the entire study. Fasting plasma samples for metabolic parameters were collected and carotid-intima media thickness (cIMT) was assessed by B-mode real-time ultrasound at baseline and every 6 months thereafter.ResultsThere was a significant reduction in waist circumference, body mass index, fasting glycemia, HbA1c, total- and LDL-cholesterol, triglycerides, and cIMT during the 18-month follow-up. Correlation analysis showed a significant association between changes in cIMT and triglycerides (r = 0.362; p < 0.0001). The MetS prevalence significantly reduced during the study, and the 26% of subjects no longer fulfilled the criteria for the MetS after 18 months.ConclusionsLiraglutide improves cardio-metabolic risk factors in subjects with the MetS in a real-world study. Trial Registration ClinicalTrials.gov: NCT01715428.

Liraglutide Treatment Reduces Endothelial Endoplasmic Reticulum Stress and Insulin Resistance in Patients With Diabetes Mellitus

“…Patients with DM have multiple systemic risk factors that likely contribute together to the endothelial phenotype observed, including differences in lipid profile. Prior studies have shown that administration of GLP‐1 agonists has an impact on lipid homeostasis 72, 73, 74, 75. Liraglutide administration appears to have beneficial effects on plasma lipids and lipoproteins, including a reduction in total cholesterol, triglycerides, and low‐density lipoprotein cholesterol, and an increase in high‐density lipoprotein cholesterol 76, 77, 78.…”

GLP-1 receptor agonists, carotid atherosclerosis and retinopathy

“…Liraglutide treatment was associated with normalization of cIMT values into a normal range and decreased overall prevalence of MetS. Yet, a significant association between cIMT changes and the disappearance of the MetS has been found, while triglycerides level was the only parameter with a predictive role for changes in cIMT [5]. In addition, regression in atherosclerosis induced by liraglutide has been suggested to contribute to the significant CV benefit seen in the LEADER study [2].…”

“…This points to the effect through metabolic traits associated with T2DM. Furthermore, patients with the MetS had a better response to GLP-1RA treatment compared to those who did not fulfill the criteria for the MetS, as well as to those with T2DM only [5]. Although the underlying mechanisms are still unclear, it may be explained, at least in part, by the alterations of gene and protein expressions involved in glucose and lipid metabolism [20], by the effects through metabolic and adiposity pathways (including adipose distribution, and ectopic (hepatic and pancreatic) fat deposition [21]).…”

“…Liraglutide, a widely prescribed GLP-1RA, exerts several beneficial non-glycemic effects improving various cardiometabolic risk markers, including a surrogate marker of early, subclinical atherosclerosis, carotid-intima media thickness (cIMT), in subjects with T2DM, but also in those with the metabolic syndrome (MetS), as it has been shown recently in an 18-months real-world study [5]. Liraglutide treatment was associated with normalization of cIMT values into a normal range and decreased overall prevalence of MetS.…”

“…Although the underlying mechanisms are still unclear, it may be explained, at least in part, by the alterations of gene and protein expressions involved in glucose and lipid metabolism [20], by the effects through metabolic and adiposity pathways (including adipose distribution, and ectopic (hepatic and pancreatic) fat deposition [21]). Also, the effects on oxidative stress, inflammation, and atherogenic lipoproteins should not be neglected [5].…”