incretins and Carotid-Artery-Diseases

The mechanism behind the cardiovascular protection observed with human GLP-1 RA (glucagon-like peptide-1 receptor agonists) in type 2 diabetes is unknown. We hypothesized that treatment with the GLP-1 RA liraglutide had a positive effect on vascular inflammation.

Topics: Aged; Biomarkers; Blood Glucose; Carotid Artery Diseases; Carotid Intima-Media Thickness; Coronary Angiography; Coronary Artery Disease; Denmark; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fluorodeoxyglucose F18; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Liraglutide; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Radiopharmaceuticals; Time Factors; Treatment Outcome; Vasculitis

Exenatide, a glucagon like peptide 1 analog, has been suggested to reduce the cardiovascular disease risk factors, such as body weight, blood pressure and subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). This was the first randomized, open-label, controlled trial to compare the effects of exenatide versus insulin on subclinical atherosclerosis, as assessed by carotid-intima media thickness (CIMT), in patients with T2DM.. A total of 66 patients with T2DM admitted from March 10, 2015 to June 20, 2017 in the Department of Endocrinology, Beijing Hospital were randomized to receive twice-daily exenatide or aspartate 70/30 insulin for 52 weeks. The primary endpoint was change from baseline in CIMT, and secondary endpoints included changes at week 52 from baseline in body weight, glycemic markers, lipid metabolism markers, blood pressure, C-reactive protein, fibrinogen, 8-hydroxydeoxyguanosine, irisin, and brain natriuretic peptide.. Exenatide more significantly reduced the CIMT from baseline compared with insulin after 52 weeks, with a mean difference of - 0.14 mm (95% interval confidence: - 0.25, - 0.02; P = 0.016). Weight and body mass index were both significantly reduced in the exenatide group over 52 weeks. Exenatide reduced total lipoprotein and low-density lipoprotein cholesterol levels more significantly than insulin at weeks 16 and 40. Correlation analyses showed that CIMT was positively correlated with low-density lipoprotein cholesterol.. Twice-daily exenatide could prevent atherosclerosis progression in patients with T2DM over a 52-week treatment period compared with insulin therapy. Trial registration Chinese Clinical Trial Registry ChiCTR-1800015658.

Topics: Adult; Aged; Beijing; Blood Glucose; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Disease Progression; Drug Administration Schedule; Exenatide; Female; Humans; Hypoglycemic Agents; Incretins; Insulin Aspart; Male; Middle Aged; Predictive Value of Tests; Time Factors; Treatment Outcome; Young Adult

Liraglutide, 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.. We 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.. There 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.. Liraglutide improves cardio-metabolic risk factors in subjects with the MetS in a real-world study. Trial Registration ClinicalTrials.gov: NCT01715428.

Topics: Aged; Biomarkers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Echocardiography, Doppler, Color; Female; Humans; Hypoglycemic Agents; Incretins; Italy; Liraglutide; Male; Metabolic Syndrome; Metformin; Middle Aged; Predictive Value of Tests; Prevalence; Prospective Studies; Risk Factors; Treatment Outcome