Background & aim: Neurodegenerative diseases are characterized by complex, large-scale structural and cellular alterations across the brain. Understanding these changes requires comprehensive, whole-brain analysis at high spatial resolution. Three-dimensional light sheet fluorescence microscopy (3D LSFM) enables rapid imaging of intact…
Abstract: Survodutide is a novel GCG/GLP-1 receptor (GCGR/GLP-1R) dual agonist in clinical development for people with obesity and people with metabolic dysfunction-associated steatohepatitis (MASH). Preclinically, survodutide demonstrated body weight lowering efficacy through decreased energy intake and increased energy expenditure. Here,…
Background: Injectable peptide-based glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RAs) are effective treatments for obesity and diabetes but are limited by patient compliance and scalability challenges. In contrast, non-peptide small-molecule GLP1RAs offer the advantage of oral delivery but are relatively inactive…
Background & aim: Glucagon-like peptide-1 receptor agonists, such as semaglutide, induce substantial weight loss but may adversely affect muscle mass. This is of particular concern in older adults with obesity, who are vulnerable to sarcopenia. Accordingly, obesity treatments should be…
Background & aim: Subcutaneous pump delivery of the GLP1-receptor-agonist exenatide reduced body weight and improved glycemia in the DIO mouse. Basal-bolus administration conferred advantage over basal alone. This mode of incretin-based therapy offers an alternative to conventional intermittent dosing and…
Background & aim: Accurate assessment of muscle mass remains a major challenge in preclinical models of sarcopenia, obesity, and drug-induced atrophy. Traditional readouts such as lean mass from body composition scans lack spatial resolution and anatomical specificity, especially in conditions…
Background & aim: Nutrient-stimulated gut hormone peptide YY3e36 (PYY3e36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy…
Background & aim: Survodutide is a dual agonist of the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), currently in clinical development for obesity and related metabolic disorders. By concurrently enhancing GCGR and GLP1R signaling, survodutide offers a synergistic approach…
Background & aim: Injectable peptide-based GLP-1 receptor agonists (GLP1RAs) are effective treatments for obesity and type 2 diabetes, yet present challenges related to patient compliance and scalable production. In contrast, small-molecule GLP1RAs offer significant advantages, including oral bioavailability and scalable…
