Tesamorelin improves fat quality independent of changes in fat quantity.

Objectives: Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density.

Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV.

Objective: Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Design And Methods: We utilized data from two multicenter Phase III trials of tesamorelin among 806 HIV-infected patients with abdominal obesity.

Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial.

Objective: Use of growth hormone is associated with side effects, including insulin resistance. The objective of this study was to determine whether tesamorelin, a stabilized growth hormone-releasing hormone analogue, would alter insulin sensitivity or control of diabetes.

Design: A 12-week randomized, placebo-controlled study of 53 patients with type 2 diabetes.

Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.

Background: Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy.

Objectives: 1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin.

Methods: Data were analyzed from two Phase 3 studies in which HIV-infected patients with excess abdominal fat were randomized in a 2:1 ratio to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) subcutaneously daily for 6 months, using ANOVA and ANCOVA models.

Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects.

The objective of this analysis was to characterize the time course of selected pharmacodynamic (PD) markers of tesamorelin: growth hormone (GH) and insulin-like growth factor (IGF-1) concentrations in HIV-infected patients and healthy volunteers. A total of 41 subjects in Phase I trials receiving subcutaneous daily doses of 1 or 2 mg of tesamorelin during 14 consecutive days were included in this analysis. A previous pharmacokinetic (PK) model of tesamorelin was used as the input function for the PD model of GH.

Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects.

Background And Objectives: Tesamorelin is a synthetic analogue of growth hormone-releasing factor (GRF), which increases basal and pulsatile growth hormone (GH) secretion and subsequently increases insulin-like growth factor (IGF)-1. Limited information is available about the pharmacokinetics of this compound. Consequently, the aim of this study was to characterize the population pharmacokinetics of tesamorelin in HIV-infected patients and healthy subjects.

Impact of Tesamorelin, a Growth Hormone-Releasing Factor (GRF) Analogue, on the Pharmacokinetics of Simvastatin and Ritonavir in Healthy Volunteers.

The potential impact of tesamorelin on CYP3A activity was investigated by examining its effect on the pharmacokinetics of simvastatin and ritonavir. In two randomized, two-way crossover studies, subjects were administered 2 mg tesamorelin on Days 1-7 with 80 mg simvastatin or 100 mg ritonavir co-administered on Day 6 (Treatment A), and a single dose of simvastatin or ritonavir alone on Day 6 (Treatment B). Pharmacokinetic samples were collected on Day 6 to measure simvastatin, ritonavir and tesamorelin plasma concentrations.

Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.

Background: Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes.

Methods: In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks.

Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction.

Objective: To report the effects of tesamorelin, a growth hormone-releasing hormone analogue, on inflammatory and fibrinolytic markers and to relate these effects to changes in visceral adipose tissue (VAT).

Design And Methods: Four hundred and ten HIV-infected patients with abdominal adiposity were randomized to 2 mg tesamorelin (n = 273) or placebo (n = 137) subcutaneously daily for 26 weeks. Circulating plasminogen activator inhibitor-1 (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, C-reactive protein (CRP), and adiponectin were assessed.

Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data.

Context: HIV patients treated with antiretroviral therapy (ART) often develop increased visceral adipose tissue (VAT).

Objective: Our objective was to perform a pooled analysis of two phase-3 studies of tesamorelin in ART-treated HIV patients with excess abdominal fat.

Design And Setting: Two multicenter, international studies were conducted; a 26-wk randomized, placebo-controlled primary intervention phase was followed by a 26-wk safety extension.

Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension.

Background: HIV-infected patients receiving antiretroviral therapy often demonstrate excess visceral fat. A growth hormone-releasing factor, tesamorelin, may selectively reduce visceral fat in this population. We investigated the effects of tesamorelin (GHRH(1-44)) in HIV-infected patients with central fat accumulation.

Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation.

Objective: Treatment of HIV patients with daily tesamorelin, a growth hormone-releasing factor analogue, for 26 weeks resulted in a significant decrease in visceral adipose tissue (VAT) and improvement in lipids. The objective of the 26-week extension phase was to evaluate long-term safety and effects of tesamorelin.

Design: HIV patients with central fat accumulation in the context of antiretroviral therapy were randomized to tesamorelin 2 mg (n = 273) or placebo (n = 137) s.

Gliclazide inhibits differentiation-associated biologic events in human monocyte-derived macrophages.

We investigated the in vitro effect of gliclazide on human monocyte-derived macrophage scavenger receptor expression and activity, foam cell formation, and lipopolysaccharide-induced cytokine production. Differentiation of human monocytes into macrophages in the presence of gliclazide (1-10 microg/mL) decreased CD36 expression by 20% to 50%, with maximal effect occurring at 2.5 microg/mL (P<.

The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy.

Objective: In view of the association of hyperprolactinaemia with insulin resistance, we hypothesized that patients with hyperprolactinaemia may present increased cardiovascular risk markers.

Design: Descriptive clinical trial.

Methods: Serum glucose, insulin, insulin resistance, lipids, high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and soluble E-selectin (sELAM-1) serum levels were determined in 15 patients with hyperprolactinaemia at baseline (compared with 20 healthy subjects) and after 12 weeks of cabergoline therapy (0.

Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin.

Accumulating evidence suggests that high concentrations of leptin observed in obesity and diabetes may contribute to their adverse effects on cardiovascular health. Metformin monotherapy is associated with reduced macrovascular complications in overweight patients with type 2 diabetes. It is uncertain whether such improvement in the cardiovascular outcome is related to specific vasculoprotective effects of this drug.

Benefits of gliclazide in the atherosclerotic process: decrease in monocyte adhesion to endothelial cells.

Atherosclerotic cardiovascular disease is the leading cause of premature death in patients with diabetes. Atherosclerosis is a chronic immune-mediated disease, the initiation, progression, and destabilization of which is driven and regulated by inflammatory cells. One critical event in the initiation of this vascular inflammatory disease is the adhesion of leukocytes to the activated endothelium and their migration into the vessel wall.

Monocyte adhesion in diabetic angiopathy: effects of free-radical scavenging.

Increased interaction of monocytes with vascular cells is linked to the development and progression of atherosclerosis in patients with diabetes. One major determinant of increased monocyte binding to vascular cells could be oxidative stress. Given the free-radical scavenging properties of gliclazide, we evaluated the ex vivo and in vitro effects of this drug on human monocyte binding to endothelial cells and smooth muscle cells (SMCs).

Advanced glycation end products increase, through a protein kinase C-dependent pathway, vascular endothelial growth factor expression in retinal endothelial cells. Inhibitory effect of gliclazide.

Accumulating evidence points to a causal role for advanced glycation end products (AGEs) in the development of diabetic vascular complications, including retinopathy. Possible pathogenic mechanisms linking AGEs to diabetic retinopathy include protein kinase C (PKC) activation, oxidative stress, and vascular endothelial growth factor (VEGF) expression. In the present study, we investigated the effect of AGEs on VEGF expression in bovine retinal endothelial cells (BRECs) and determined the role of PKC and oxidative stress in this effect.