LAR Exenatide

BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood...

AIM: To evaluate the albuminuria-lowering effect of dapagliflozin, exenatide, and the combination of dapagliflozin and exenatide in patients with type 2 diabetes and microalbuminuria or macroalbuminuria. METHODS: Participants with type 2 diabetes, an estimated glomerular filtration rate (eGFR) of more than 30 ml/min/1.73m2 and an urinary albumin: creatinine ratio (UACR) of more than 3.5 mg/mmol and 100 mg/mmol or less completed three 6-week treatment periods, during which dapagliflozin 10 mg/d, exenatide 2 mg/wk and both drugs combined were given in random order...

INTRODUCTION: Coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) are associated with risk of death, as well as brain, heart and kidney injury. Glucagon-like peptide-1 (GLP-1) analogues are approved for treatment of type 2 diabetes, and GLP-1 analogues have been suggested to have potential organ-protective and anti-inflammatory effects. During cardiopulmonary bypass (CPB), consensus on the optimal fraction of oxygen is lacking. The objective of this study is to determine the efficacy of the GLP-1-analogue exenatide versus placebo and restrictive oxygenation (50% fractional inspired oxygen, FiO2) versus liberal oxygenation (100% FiO2) in patients undergoing open heart surgery...

This communication provides a contemporary classification of glucagon-like peptide 1 receptor agonists (GLP1RAs) based on indication, route, and frequency of administration, which could support a person-centric approach to treatment choice. It includes all recently developed GLP1RAs as well as those in advanced stages of clinical study. Keeping pace with current trends in pharmacology and metabolic medicine, it attempts to bring clarity and simplicity to a complex spread of information.

BACKGROUND: Diabetes is 3-4 times more prevalent in Indigenous Australians with blood glucose levels often above target range. Once weekly formulations of exenatide(exenatide-LAR) have demonstrated significantly greater improvements in glycaemic management with no increased risk of hypoglycaemia and with reductions in bodyweight but have not been studied in Indigenous Australians. AIMS: To assess the feasibility and metabolic effects of once weekly supervised injection of exenatide-LAR in addition to standard care in Indigenous Australians with type 2 diabetes...

GLP-1 agonists have become increasingly interesting as a new Parkinson's disease (PD) clinical treatment strategy. Additional preclinical studies are important to validate this approach and define the disease stage when they are most effective. We hence characterized the efficacy of PT320, a sustained release formulation of the long acting GLP-1 agonist, exenatide, in a progressive PD (MitoPark) mouse model. A clinically translatable biweekly PT320 dose was administered starting at 5 weeks of age and longitudinally evaluated to 24 weeks, and multiple behavioral/cellular parameters were measured...

Rationale: Increased myocardial activity of Ca/calmodulin-dependent kinase II (CaMKII) leads to heart failure (HF) and arrhythmias. In Drosophila neurons, interaction of CaMKII with Ca/CaM-dependent serine protein kinase (CASK) has been shown to inhibit CaMKII activity, but the consequences of this regulation for HF and ventricular arrhythmias are unknown. Objective: We hypothesize that CASK associates with CaMKII in human and mouse hearts thereby limiting CaMKII activity, and that altering CASK expression in mice changes CaMKII activity accordingly, with functional consequences for contractile function and arrhythmias...

Bydureon® (Bdn) is a once-weekly injectable long-acting release (LAR) product for adults with type 2 diabetes based on PLGA microspheres encapsulating the glucagon like peptide (GLP-1) analog, exenatide. Despite its widespread use in type 2 diabetes treatment, little information has been published concerning the physical-chemical aspects and exenatide stability in this product. Here, we developed and validated methods to evaluate attributes and performance of Bdn such as particle size/size distribution and residual levels of moisture and organic solvent(s)...

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists differ in their structure and duration of action and have been studied in trials of varying sizes and with different patient populations, with inconsistent effects on cardiovascular outcomes reported. We aimed to synthesise the available evidence by doing a systematic review and meta-analysis of cardiovascular outcome trials of these drugs. METHODS: We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials for eligible placebo-controlled trials reporting major adverse cardiovascular events (MACE; ie, cardiovascular death, stroke, or myocardial infarction) up to June 15, 2019...

Two elderly patients with poorly controlled type 2 diabetes mellitus had difficulty self-managing their medications. Exenatide long-acting release (LAR), with an extended administration interval of 1 month, maintained hemoglobin A1c (HbA1c) level in the 7% range. Monthly administration of exenatide-LAR may be considered for use in carefully selected elderly individuals.

Objective: Semaglutide is a glucagon-like peptide 1 (GLP-1) analog for the once-weekly treatment of type 2 diabetes (T2D). In the global SUSTAIN clinical trial program, semaglutide demonstrated superior glycated hemoglobin (HbA1c ) and body weight reductions versus comparators. This post hoc analysis compared the proportion of patients achieving combined reductions in glycemia and body weight versus comparators. Methods: A total of 5,119 subjects with T2D in the phase 3 SUSTAIN 1 through 5 and 7 trials, from 33 countries, were included in this post hoc analysis...

AIM: To evaluate the effect of exenatide long acting release (LAR) on carotid intima-media thickness (IMT) and endothelial function in patients with type 2 diabetes mellitus. METHODS: Sixty subjects with type 2 diabetes mellitus were treated with exenatide LAR as add-on to stable doses of metformin for 8 months in an open label study. Anthropometric variables, lipid profile and glycemic parameters were assessed by routine analysis. Carotid IMT by Doppler ultrasound and endothelial function by flow-mediated dilation of the brachial artery were also assessed...

Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results...

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...

OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm...

In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications. Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk...

Several GLP-1 receptor agonists are currently available for treatment of type 2 diabetic patients. Based on their pharmacokinetic/pharmacodynamic profile, these drugs are classified as short-acting GLP-1 receptor agonists (exenatide and lixisenatide) or long-acting GLP-1 receptor agonists (exenatide-LAR, liraglutide, albiglutide, and dulaglutide). In clinical practice, they are also classified as basal or prandial GLP-1 receptor agonists to differentiate between patients who would benefit more from one or another based on characteristics such as previous treatment and the predominance of fasting or postprandial hyperglycemia...

While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms)...

AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched...

BACKGROUND: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising results in the treatment of type 2 diabetes. Herein, we compared the efficacy and safety of once-weekly GLP-1RAs with exenatide and liraglutide separately. METHODS: We systematically surveyed the pertinent literature using various databases. The randomised controlled trials that compared once-weekly GLP-1RAs with exenatide and liraglutide in type 2 diabetes were included...